View source for Propylhexedrine

{{Short description|Topical nasal decongestant}}
{{good article}}
{{Use dmy dates|date=September 2021}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Verifiedfields     = changed
| Watchedfields      = changed
| verifiedrevid      = 464217507
| drug_name          = Propylhexedrine
| IUPAC_name         = (±)-1-cyclohexyl-''N''-methylpropan-2-amine
| image              = Propylhexedrine.svg
| imageL             = Propylhex_3d.png
| widthL             = 
| altL               = 
| imageR             = Propylhex_3d (R).png
| widthR             = 
| altR               = 
| captionLR          = Left: (''S'')-Propylhexedrine<br/>Right: (''R'')-Propylhexedrine

<!--Clinical data-->| tradename          = Benzedrex, Obesin, Dristan Inhaler, and others
| Drugs.com          = {{drugs.com|monograph|propylhexedrine}}
| pregnancy_category = C
| legal_AU           = S4
| legal_BR           = B1
| legal_BR_comment   = 
| legal_CA           = Unscheduled
| legal_DE           = [[Prescription drug|Prescription Only]]
| legal_US           = OTC
| legal_UN           = Unscheduled
| legal_UK           = P
| routes_of_administration = Medical: [[Intranasal]] (inhaler)<br />Recreational: Oral and [[parenteral]] routes

<!--Pharmacokinetic data-->| bioavailability    = 
| protein_bound      = 
| metabolism         = 
| elimination_half-life = 4 ± 1.5 hours
| excretion          = <!--Identifiers-->
| index2_label       = hydrochloride
| CAS_number_Ref     = {{cascite|correct|CAS}}
| CAS_number         = 101-40-6
| CAS_number2_Ref    = {{cascite|correct|CAS}}
| CAS_number2        = 1007-33-6
| ATC_prefix         = N06BA
| ATC_suffix         = 
| ATC_supplemental   = 
| PubChem            = 7558
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB06714
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 7277
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = LQU92IU8LL
| UNII2_Ref          = {{fdacite|correct|FDA}}
| UNII2              = 064LUN7NZ5
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D05637
| synonyms           = {{ubl|Hexahydrodesoxyephedrine|Cyclohexylisopropylmethylamine|1-cyclohexyl-2-methylaminopropane}}
| C                  = 10
| H                  = 21
| N                  = 1
| SMILES             = N(C(CC1CCCCC1)C)C
| StdInChI_Ref       = {{stdinchicite|correct|chemspider}}
| StdInChI           = 1S/C10H21N/c1-9(11-2)8-10-6-4-3-5-7-10/h9-11H,3-8H2,1-2H3
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = JCRIVQIOJSSCQD-UHFFFAOYSA-N
| chirality          = [[Racemic mixture]]
}}

'''Propylhexedrine''', commonly sold under the brand name '''Benzedrex''', is an [[Psychotropic alkylamines|alkylamine]] primarily utilized as a [[Topical decongestant|topical nasal decongestant]].<ref>{{Cite web |date=June 7, 2023 |title=Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=341.20 |archive-url=https://web.archive.org/web/20230706041627/https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=341.20 |archive-date=6 July 2023 |access-date=July 5, 2023 |website=[[FDA]] }}</ref> Its main indications are relief of congestion due to [[Common cold|colds]], [[Allergy|allergies]], and allergic [[rhinitis]].<ref name="Daily Med">{{Cite web |title=BENZEDREX 09-19-2014- propylhexedrine inhalant |url=https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=03a8ef3c-a808-6208-e054-00144ff8d46c |archive-url=https://archive.today/20230716000914/https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=03a8ef3c-a808-6208-e054-00144ff8d46c |archive-date=July 16, 2023 |access-date=July 15, 2023 |work=Daily Med |publisher=U.S. National Library of Medicine}}</ref> Propylhexedrine was first used medically in 1949, with the release of Benzedrex by [[Smith, Kline & French]], and it has been used, mainly within the United States, since then.<ref name="Schwarez" />

==Medical use==
Propylhexedrine is used to treat acute [[nasal congestion]] related to the [[cold|common cold]], [[allergies]] and [[hay fever]]. For nasal congestion, the dosage is listed as four inhalations (two inhalations per nostril) every two hours for adults and children 6–12 years of age. Each inhalation delivers 0.4 to 0.5 milligrams (400 to 500 [[micrograms|''μ''g]]) in 800 [[Litre|millilitre]]s of air.<ref name="B. F. Ascher and Company" /><ref name="Daily Med" /><ref name="www.pharmacopeia.cn" /> Use is not to exceed three days.<ref name="Daily Med" />

Historically, it has also been used for [[weight loss]] in oral tablet preparations at a dose of 25 milligrams.<ref name="Rose_1959" /><ref>{{cite journal | vauthors = Docherty JR | title = Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA) | journal = British Journal of Pharmacology | volume = 154 | issue = 3 | pages = 606–622 | date = June 2008 | pmid = 18500382 | pmc = 2439527 | doi = 10.1038/bjp.2008.124 }}</ref> No medications containing propylhexedrine are currently approved for weight loss in any country since roughly 1976.<ref name="Winter_1976" />

==Contraindications==
Propylhexedrine should not be used if a [[MAOI]] has been used in the past 14 days or is currently in use by a person.<ref name="Daily Med" />

Unlike other [[topical decongestant]]s, propylhexedrine is not required to carry a warning against use in individuals with hypertension.<ref>{{Cite journal | vauthors = Terrie YC |date=December 20, 2017 |title=Decongestants and Hypertension: Making Wise Choices When Selecting OTC Medications |url=https://www.pharmacytimes.com/view/decongestants-and-hypertension-making-wise-choices-when-selecting-otc-medications |url-status=live |archive-url=https://web.archive.org/web/20230130120554/https://www.pharmacytimes.com/view/decongestants-and-hypertension-making-wise-choices-when-selecting-otc-medications |archive-date=January 30, 2023 |access-date=November 13, 2023 |website=Pharmacy Times|series=December 2017 Heart Health |volume=83 }}</ref>

Propylhexedrine is not recommended in individuals younger than six years of age.<ref>{{Cite web |title=Propylhexedrine |url=https://www.mskcc.org/cancer-care/patient-education/medications/adult/propylhexedrine |archive-url=https://archive.today/20230809073320/https://www.mskcc.org/cancer-care/patient-education/medications/adult/propylhexedrine |archive-date=August 9, 2023 |access-date=2023-07-16 |website=www.mskcc.org |publisher=Memorial Sloan Kettering Cancer Center |language=en}}</ref> There is at least one case of reported accidental poisoning resulting from child access to a propylhexedrine product.<ref name="Polster_1965" />

== Adverse effects ==
When used as an inhaler, the most common adverse effects warned about for propylhexedrine are temporary discomfort (e.g., stinging or burning sensations) or [[rebound congestion]].<ref name="Daily Med" /> The sharing of propylhexedrine inhalers may spread infection.<ref name="Daily Med" /> The occurrence of these adverse effects is uncommon as propylhexedrine is [[generally recognized as safe and effective]].<ref name="FDA_2021">{{Cite web |date=March 25, 2021 |title=Benzedrex (propylhexedrine): Drug Safety Communication |url=https://www.fda.gov/safety/medical-product-safety-information/benzedrex-propylhexedrine-drug-safety-communication-fda-warns-abuse-and-misuse-nasal-decongestant |archive-url=https://archive.today/20230807212835/https://www.fda.gov/safety/medical-product-safety-information/benzedrex-propylhexedrine-drug-safety-communication-fda-warns-abuse-and-misuse-nasal-decongestant |archive-date=August 7, 2023 |access-date=July 16, 2023 |website=[[FDA]]}}</ref> However, the use of propylhexedrine products in manners not intended by their labeling can result in severe adverse effects not typically encountered in therapeutic settings.<ref name="Center for Drug Evaluation and Research_2021" /><ref name="National Pharmacy & Therapeutics Committee_2021" /><ref name="Parrish_2022" /> The outcomes of improperly using propylhexedrine products can include hospitalization, disability, or even death.<ref name="FDA_2021" /> Public health agencies such as the [[FDA]] have advised propylhexedrine products only be used in the manners directed on their label.<ref name="FDA_2021" />

== Overdose ==
Reports of overdoses from propylhexedrine have been documented, but they are uncommon.<ref name="Smith_1988" /> Most instances of overdoses attributed to propylhexedrine have been the result of improper use of a propylhexedrine product in a manner not intended by its labeling for (non-medical) [[Recreational drug use|recreational purposes]].<ref name="Center for Drug Evaluation and Research_2021">{{Cite web |author=Center for Drug Evaluation and Research |date=2021-04-15 |title=FDA warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-abuse-and-misuse-nasal-decongestant-propylhexedrine-causes-serious-harm |url-status=dead |archive-url=https://web.archive.org/web/20230223010114/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-abuse-and-misuse-nasal-decongestant-propylhexedrine-causes-serious-harm |archive-date=23 February 2023 |access-date=July 8, 2023 |website=[[FDA]] |publisher=U.S. Food and Drug Administration |language=en}}</ref> As noted by the [[FDA]], the most common symptoms of propylhexedrine overdose are the following: "...[R]apid heart rate, agitation, high blood pressure, chest pain, tremor, hallucinations, delusions, confusion, nausea, and vomiting."<ref name="Center for Drug Evaluation and Research_2021" /> The use of propylhexedrine products in manners inconsistent with their labeling has proven fatal in some cases.<ref name="Sturner_1974" /><ref>{{Cite news |date=1985-09-22 |title=Rise In Nasal Inhaler Abuse Worries Officials |language=en-US |pages=34 |work=[[The New York Times]] |url=https://www.nytimes.com/1985/09/22/us/rise-in-nasal-inhaler-abuse-worries-officials.html |url-status=live |access-date=2023-08-30 |archive-url=https://archive.today/20230830042034/https://www.nytimes.com/1985/09/22/us/rise-in-nasal-inhaler-abuse-worries-officials.html |archive-date=August 30, 2023 |issn=0362-4331}}</ref> Propylhexedrine products are considered to be safe and effective if used as intended.<ref name="Center for Drug Evaluation and Research_2021" /> Regardless, medical attention should be sought in the case of suspected overdose.<ref name="National Capital Poison Control" />

== Interactions ==
Most of propylhexedrine's interactions with other medications have to do with its ability to constrict blood vessels. Propylhexedrine’s most serious interaction is with [[Monoamine oxidase inhibitor|monoamine oxidase inhibitors]], which are contraindicated.<ref name="Daily Med" /> Monoamine oxidase inhibitors are used, albeit uncommonly, as an antidepressant.<ref>{{Cite web |title=Monoamine oxidase inhibitors |url=https://www.mayoclinic.org/diseases-conditions/depression/in-depth/maois/art-20043992 |access-date=2024-05-15 |website=Mayo Clinic |language=en}}</ref> Nonetheless, caution should be exercised when administering propylhexedrine concurrently with other medicines.

==Pharmacology==

=== Mechanism of action ===
Propylhexedrine works mainly as an [[Alpha-adrenergic agonist|adrenergic agonist]], when used at therapeutic doses in an inhaler dosage form.<ref name="DB">{{cite web |title=Propylhexedrine |url=http://www.drugbank.ca/drugs/DB06714 |url-status=dead |archive-url=https://web.archive.org/web/20120315115006/http://www.drugbank.ca/drugs/DB06714 |archive-date=15 March 2012 |access-date=July 8, 2023 |work=DrugBank}}</ref> This [[Vasoconstriction|restricts the blood vessels]] in the nose and reduces swelling; thereby, it relieves [[nasal congestion]].<ref>{{Cite web |date=2017-10-18 |title=Decongestants |url=https://www.nhs.uk/conditions/decongestants/ |archive-url=https://archive.today/20230809064415/https://www.nhs.uk/conditions/decongestants/ |archive-date=August 9, 2023 |access-date=2023-08-09 |website=[[National Health Service]] |language=en}}</ref> At higher doses, propylhexedrine affects the [[central nervous system]] as a [[norepinephrine–dopamine releasing agent]].<ref name="Teja_2020" /> Propylhexedrine likely exerts such effects in a manner similar to related [[Psychotropic alkylamines|alkylamines]] such as [[cyclopentamine]], [[methylhexanamine]], and [[tuaminoheptane]].<ref>{{cite journal | vauthors = Small C, Cheng MH, Belay SS, Bulloch SL, Zimmerman B, Sorkin A, Block ER | title = The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 386 | issue = 2 | pages = 266–273 | date = August 2023 | pmid = 37348963 | pmc = 10353075 | doi = 10.1124/jpet.122.001573 }}</ref><ref name="pmid14209515">{{cite journal | vauthors = Schmidt JL, Fleming WW | title = A Nonsympathomimetic Effect of Cyclopentamine and Beta-Mercaptoethylamine in the Rabbit Ileum | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 145 | pages = 83–86 | date = July 1964 | pmid = 14209515 }}</ref><ref name="pmid2386550">{{cite journal | vauthors = Delicado EG, Fideu MD, Miras-Portugal MT, Pourrias B, Aunis D | title = Effect of tuamine, heptaminol and two analogues on uptake and release of catecholamines in cultured chromaffin cells | journal = Biochemical Pharmacology | volume = 40 | issue = 4 | pages = 821–825 | date = August 1990 | pmid = 2386550 | doi = 10.1016/0006-2952(90)90322-c }}</ref> In addition, propylhexedrine further releases monoamines through [[TAAR1 agonist|TAAR1 agonism]] and [[VMAT2]] inhibition.<ref name="DB" /> Propylhexedrine also exhibits [[Antihypotensive agent|antihypotensive]] effects.<ref name = "Lands_1947">{{cite journal | vauthors = Lands AM, Nash VL | title = The pharmacologic activity of N-methyl-beta-cyclohexyl-isopropylamine hydrochloride | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 89 | issue = 4 | pages = 382–385 | date = April 1947 | pmid = 20295519 | url = https://jpet.aspetjournals.org/content/89/3/382 }}</ref>

===Pharmacokinetics===
[[File:Propylhexedrine_metabolism.svg|thumb|400px|Metabolism of propylhexedrine<ref name = "Midha_1974" />]]
Propylhexedrine undergoes metabolism via N-demethylation, C-oxidation, N-oxidation, dehydrogenation, and hydrolysis to form various metabolites such as [[norpropylhexedrine]], cyclohexylacetoxime, [[cyclohexylacetone]], and 4-hydroxypropylhexedrine.<ref name = "Midha_1974">{{cite journal | vauthors = Midha KK, Beckett AH, Saunders A | title = Identification of the major metabolites of propylhexedrine in vivo (in man) and in vitro (in guinea pig and rabbit) | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 4 | issue = 10 | pages = 627–635 | date = October 1974 | pmid = 4428789 | doi = 10.1080/00498257409169765 }}</ref>
{{clear}}

==Chemistry==
[[File:PropylhexedrineHCl.jpg|thumb|[[Hydrochloride]] salt of propylhexedrine. The off-brown color gives rise to the slang term for this salt: "peanut butter".<ref>{{cite journal | vauthors = Schaiberger PH, Kennedy TC, Miller FC, Gal J, Petty TL | title = Pulmonary hypertension associated with long-term inhalation of "crank" methamphetamine | journal = Chest | volume = 104 | issue = 2 | pages = 614–616 | date = August 1993 | pmid = 8101799 | doi = 10.1378/chest.104.2.614 }}</ref>]]
[[Free base|Freebase]] propylhexedrine is a volatile, oily liquid at room temperature. The slow [[evaporation]] of freebase propylhexedrine allows it to be administered via inhalation.<ref>{{cite patent|country=US|number=4095596|title=Nasal Inhaler|status=granted|gdate=20 June 1978|inventor=Grayson M |assign1=Smithkline Corp. | url = https://patents.google.com/patent/US4095596A/en }}</ref> The evaporation of the freebase also accounts for the limited shelf-life of propylhexedrine inhalers. Many of the [[salt (chemistry)|salt]]s of propylhexedrine are stable, clear to off-white crystalline substances that readily dissolve in water.<ref>{{cite journal | vauthors = Mancusi-Ungaro HR, Decker WJ, Forshan VR, Blackwell SJ, Lewis SR | title = Tissue injuries associated with parenteral propylhexedrine abuse | journal = Journal of Toxicology. Clinical Toxicology | volume = 21 | issue = 3 | pages = 359–372 | year = 1983 | pmid = 6144800 | doi = 10.1097/00005373-198307000-00114 }}</ref>

Propylhexedrine is similar in chemical structure to [[phenylethylamines]]. Phenylethylamines and [[substituted phenethylamine]]s are found in the core of many [[trace amine]]s and [[sympathomimetic drug]]s. The main difference is the presence of an [[alicyclic]] [[cyclohexane|cyclohexyl]] group instead of the [[Aromatic compound|aromatic]] [[phenyl]] group of a [[phenylethylamines|phenethylamine]].
:[[File:CycloalkylamineSim.svg|300px]]

Propylhexedrine is a [[Chirality (chemistry)|chiral]] compound. The active ingredient contained in Benzedrex inhalers is [[racemic]] (''RS'')-propylhexedrine as the free base.<ref name="B. F. Ascher and Company" /> (''S'')-Propylhexedrine, also known as [[levopropylhexedrine]], is believed to be the more biologically active isomer of the two.<ref name="Lands_1947" /> The [[dextrorotatory]] counterpart, which is mainly unused, is dextropropylhexedrine.
{{clear}}
===Synthesis===
Propylhexedrine can be synthesized from [[cyclohexylacetone]] through the [[reductive amination]] of an intermediary [[imine]] over [[Amalgam (chemistry)|an aluminum-mercury amalgam]] in the presence of a hydrogen source.<ref>{{cite book | vauthors = Lednicer D, Mitscher LA |title=Organic Chemistry of Drug Synthesis |date=1977 |publisher=Wiley |isbn=978-0-471-52141-9 |volume=1 |location=New York, NY |page=37}}</ref>
:[[File:Propylhexedrine synthesis from cyclohexylacetone.svg|450px]]

However, propylhexedrine is more commonly prepared by the [[hydrogenation|catalytic hydrogenation]] of [[methamphetamine]] over [[Adams' catalyst]]. This transforms methamphetamine's phenyl ring to a [[cyclohexyl]] [[Moiety (chemistry)|moiety]].<ref>{{cite journal | vauthors = Zenitz BL, Macks EB, Moore ML | title = Preparation of some primary and secondary beta-cyclohexylalkylamines | journal = Journal of the American Chemical Society | volume = 69 | issue = 5 | pages = 1117–1121 | date = May 1947 | pmid = 20240502 | doi = 10.1021/ja01197a039 }}</ref>
:[[File:Propylhexedrine synthesis.svg|300px]]

=== Detection in bodily fluids ===
Due to its structure, administration of propylhexedrine can lead to false positives for [[Substituted phenethylamine|phenethylamine derivatives]] on urinalysis panels.<ref>{{cite journal | vauthors = Thurman EM, Pedersen MJ, Stout RL, Martin T | title = Distinguishing sympathomimetic amines from amphetamine and methamphetamine in urine by gas chromatography/mass spectrometry | journal = Journal of Analytical Toxicology | volume = 16 | issue = 1 | pages = 19–27 | date = 1992 | pmid = 1640694 | doi = 10.1093/jat/16.1.19 }}</ref> Propylhexedrine can be differentiated upon further analysis.<ref name="Johnson_1992">{{Cite journal | vauthors = Johnson P, Briner RC |date=October 1992 |title=A Clandestine Laboratory Extracting Propylhexedrine from Benzedrex Inhalers |url=https://bitnest.netfirms.com/external/JCLIC/2.4.25-28 |url-status=dead |journal=Journal of the Clandestine Laboratory Investigating Chemists Association |volume=2 |issue=4 |pages=25–28 |archive-url=https://web.archive.org/web/20230809075022/https://bitnest.netfirms.com/external/JCLIC/2.4.25-28 |archive-date=2023-08-09}}</ref>

== History ==
Propylhexedrine's medical use as a decongestant evolved from desires to find safer alternatives to previous agents.<ref name="Schwarez">{{Cite web | vauthors = Schwarez J |title=Sniffing Benzedrine Inhalers |url=https://www.mcgill.ca/oss/article/medical-health-and-nutrition/sniffing-benzedrine-inhalers |url-status=dead |archive-url=https://ghostarchive.org/archive/20230716000721/https://www.mcgill.ca/oss/article/medical-health-and-nutrition/sniffing-benzedrine-inhalers |archive-date=16 July 2023 |access-date=July 15, 2023 |website=Office for Science and Society |publisher=[[McGill University]] |language=en }}</ref> After searching for such an agent, Dr. Glenn E. Ullyot patented propylhexedrine as a decongestant in 1948. This patent was issued for benefit of [[Smith, Kline & French]].<ref>{{Cite patent|country=US|number=2454746A|title=Cyclohexylalkylamines|gdate=1948-11-23| inventor = Ullyot GE |assign = Smith Kline and French Laboratories Ltd. |url= https://patents.google.com/patent/US2454746A/en}}</ref> Before it was sold nationally in the United States, propylhexedrine underwent market trials in California. These market trials began on July 15, 1949.<ref name="pmid2874970" /> Propylhexedrine (under the brand name Benzedrex) was first introduced into [[interstate commerce]] on August 4, 1949.<ref>{{Cite web | vauthors = Grant G |date=August 4, 1949 |title=Extension of remarks by representative Grant on H.R. 2969 - Bezedrine Inhalers |url=https://www.govinfo.gov/content/pkg/GPO-CRECB-1949-pt15/pdf/GPO-CRECB-1949-pt15-1.pdf |url-status=live |archive-url=https://web.archive.org/web/20231029071225/https://www.govinfo.gov/content/pkg/GPO-CRECB-1949-pt15/pdf/GPO-CRECB-1949-pt15-1.pdf |archive-date=October 29, 2023 |access-date=October 29, 2023 |website=[[Govinfo.gov]] |series=Volume 95 Issue 15 |publisher=[[Government Publishing Office]] |page=A5052 |via=the [[Congressional Record]] }}</ref> 
[[File:Benzedrex-SKF.jpg|thumb|left|An early Benzedrex inhaler, {{circa|1950s}} manufactured by [[Smith, Kline & French]] that includes the synonym "1-cyclohexyl-2-methylaminopropane"]]
Approval for use in the [[United Kingdom]] soon followed in 1956.<ref name="Smith_1988" /> Later, approval for use in Canada was granted in 1998.<ref>{{Cite web |title=Propylhexedrine - NAPRA |url=https://www.napra.ca/nds/propylhexedrine/ |archive-url=https://archive.today/20230715190812/https://www.napra.ca/nds/propylhexedrine/ |archive-date=July 15, 2023 |access-date=2023-07-15 |website=(Canadian) National Association of Pharmacy Regulatory Authorities |language=en-US}}</ref> In 2023, B. F. Ascher & Co. decreased the amount of propylhexedrine in the Benzedrex inhaler from its historic 250 milligrams down to 175 milligrams.<ref>{{Cite web |title= BENZEDREX- propylhexedrine inhalant (06/23/2023) |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00d8c237-3eee-1d9f-e063-6394a90aeb86 |url-status=live |archive-url=https://archive.today/20231030224908/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=00d8c237-3eee-1d9f-e063-6394a90aeb86 |archive-date=October 30, 2023 |access-date=2023-10-30 | work = Daily Med |publisher=U.S. National Library of Medicine}}</ref>

Barbexaclone, an anticonvulsant containing propylhexedrine, was used in [[Turkey]] until its withdrawal from the market in 2009. Barbexaclone's former niche in Turkish medicine is now largely occupied by [[levetiracetam]].<ref>{{cite journal | vauthors = Bolukbasi F, Delil S, Bulus E, Senturk A, Yeni N, Karaagac N | title = End of the barbexaclone era: an experience of treatment withdrawal | journal = Epileptic Disorders | volume = 15 | issue = 3 | pages = 311–313 | date = September 2013 | pmid = 23981808 | doi = 10.1684/epd.2013.0605 | s2cid = 39112148 }}</ref>

== Manufacturing ==
The manufacture of propylhexedrine products for therapeutic use is typically performed based on guidelines established in government regulations and pharmacopeia monographs.<ref>{{Cite web |date=September 9, 1976 |title=Federal Register Vol. 41, No. 176 |url=https://www.govinfo.gov/content/pkg/FR-1976-09-09/pdf/FR-1976-09-09.pdf |archive-url=https://web.archive.org/web/20230716082330/https://www.govinfo.gov/content/pkg/FR-1976-09-09/pdf/FR-1976-09-09.pdf |archive-date=July 16, 2023 |website=[[Government Publishing Office]] |pages=38402}}</ref><ref name="www.pharmacopeia.cn">{{Cite web |title=USP Monographs: Propylhexedrine Inhalant |url=https://doi.usp.org/USPNF/USPNF_M71100_01_01.html |url-status=dead |archive-url=https://web.archive.org/web/20231227063903/https://doi.usp.org/USPNF/USPNF_M71100_01_01.html |archive-date=27 December 2023 |access-date=2023-12-27 |website=[[United States Pharmacopeia]] }}</ref>

The illicit manufacture or diversion of propylhexedrine by [[Clandestine chemistry|clandestine chemists]] for use as a recreational drug has been documented in academic literature.<ref name="Johnson_1992" /> Similar to when opioids are manufactured clandestinely for recreational use, it is unlikely that propylhexedrine produced by clandestine chemists adheres to the standards for purity, identity, and strength required of therapeutic products.<ref>{{cite journal | vauthors = Collier R | title = Street versions of opioids more potent and dangerous | journal = CMAJ | volume = 185 | issue = 12 | pages = 1027 | date = September 2013 | pmid = 23836854 | pmc = 3761004 | doi = 10.1503/cmaj.109-4535 }}</ref>

==Society and culture==
===Legal status===
==== International control ====

Propylhexedrine was placed under international control by the [[Convention on Psychotropic Substances]] in 1985. This action was reversed in 1991.<ref>{{Cite web |date=September 28, 1990 |title=Expert Committee on Drug Dependence's Twenty-Seventh Report |url=https://apps.who.int/iris/bitstream/handle/10665/40616/WHO_TRS_808.pdf?sequence=1&isAllowed=y |url-status=live |archive-url=https://web.archive.org/web/20230810175114/https://apps.who.int/iris/bitstream/handle/10665/40616/WHO_TRS_808.pdf?sequence=1&isAllowed=y |archive-date=August 10, 2023 |access-date=July 3, 2023 |website=[[World Health Organization]] |publisher=Expert Committee on Drug Dependence}}</ref>

==== Australia ====
Propylhexedrine is an S4 substance in [[Australia]].<ref>{{Cite web |title=Therapeutic Goods (Poisons Standard—June 2024) |url=https://www.health.nsw.gov.au:443/pharmaceutical/Pages/sch4d.aspx |url-status=dead |archive-url=https://archive.today/20240813153903/https://www.legislation.gov.au/F2024L00589/latest/text |archive-date=August 13, 2024 |access-date=August 13, 2024 |website=Australian Government |language=en}}</ref>

==== Brazil ====
Propylhexedrine is a Class B1 substance in [[Brazil]].<ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control |url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

==== Canada ====
Propylhexedrine was long reported to be a Schedule V substance in [[Canada]].<ref>{{Cite web |title=Erowid Propylhexedrine (Benzedrex) Vault : Law |url=https://www.erowid.org/pharms/propylhexedrine/propylhexedrine_law.shtml |url-status=dead |archive-url=https://web.archive.org/web/20230716004820/https://www.erowid.org/pharms/propylhexedrine/propylhexedrine_law.shtml |archive-date=16 July 2023 |access-date=2023-07-15 |website=[[Erowid]] }}</ref> In 2022, this status changed and propylhexedrine has since been removed from control under the [[Controlled Drugs and Substances Act]].<ref>{{Cite web |last=Government of Canada |first=Public Works and Government Services Canada |date=2022-08-31 |title=Canada Gazette, Part 2, Volume 156, Number 18: Order Amending Schedule V to the Controlled Drugs and Substances Act (Novel Fentanyl Precursors) |url=https://www.gazette.gc.ca/rp-pr/p2/2022/2022-08-31/html/sor-dors185-eng.html |url-status=live |archive-url=https://web.archive.org/web/20240331223724/https://www.gazette.gc.ca/rp-pr/p2/2022/2022-08-31/html/sor-dors185-eng.html |archive-date=2024-03-31 |access-date=2024-03-31 |website=Canada Gazette}}</ref>

==== Germany ====
Propylhexedrine is regulated as a prescription medicine in [[Germany]].<ref>{{Cite web |title=Anlage 1 AMVV - Einzelnorm |url=https://www.gesetze-im-internet.de/amvv/anlage_1.html |url-status=dead |archive-url=https://archive.today/20151130183959/http://www.gesetze-im-internet.de/amvv/anlage_1.html |archive-date=November 30, 2015 |access-date=2023-07-16 |website=[[Bundestag]]}}</ref> Initially, propylhexedrine products (namely Obesin) were available over-the-counter. However, this changed in the 1970s and propylhexedrine is now regulated as a prescription product in Germany.<ref name="Winter_1976" />

==== United Kingdom ====
It was formerly a [[Class C drug|Class C]] substance in the United Kingdom, but was deregulated in 1995.<ref>{{cite web |title=The Misuse of Drugs Act 1971 (Modification) Order 1995 |url=http://www.legislation.gov.uk/uksi/1995/1966/contents/made |archive-url=https://archive.today/20230807213717/https://www.legislation.gov.uk/uksi/1995/1966/article/2/made |archive-date=August 7, 2023 |access-date=15 June 2009 |publisher=Office of Public Sector Information}}</ref> Propylhexedrine was used recreationally during a brief period in the 1970s after increased government regulation on earlier decongestants due to misuse.<ref>{{Cite web |date=2016-03-23 |title=The blanket drugs ban is necessary, but won't solve the bigger problem – as I know from personal experience |url=http://theconversation.com/the-blanket-drugs-ban-is-necessary-but-wont-solve-the-bigger-problem-as-i-know-from-personal-experience-56237 |archive-url=https://archive.today/20240430064109/http://theconversation.com/the-blanket-drugs-ban-is-necessary-but-wont-solve-the-bigger-problem-as-i-know-from-personal-experience-56237 |archive-date=2024-04-30 |access-date=2023-11-19 |website=The Conversation |language=en-US |vauthors=Wilson A}}</ref>

==== United States ====
On the 4th of April 1988, propylhexedrine was designated a controlled substance ([[List of Schedule V drugs (US)|Schedule V]]) in the [[United States]].<ref>{{cite web | vauthors = Lawn J |date=April 4, 1988 |title=Schedules of Controlled Substances: Placement of Propylhexedrine and Pyrovalerone into Schedule V |url=https://isomerdesign.com/Cdsa/FR/53FR10869.pdf |url-status=live |archive-url=https://ghostarchive.org/archive/20221228191210/https://isomerdesign.com/Cdsa/FR/53FR10869.pdf |archive-date=28 December 2022 |access-date=9 July 2022 |website=Isomer Design |publisher=[[Drug Enforcement Administration]] }}</ref> This was done to satisfy U.S. compliance with an international treaty. However, in 1991, this action was reversed and propylhexedrine was removed from control under the Controlled Substances Act. This was based on the opinion of the [[Drug Enforcement Administration]] that propylhexedrine did not warrant control.<ref>{{cite web | vauthors = Bonner R |date=December 3, 1991 |title=Schedules of Controlled Substances: Removal of Propylhexedrine From Control |url=https://isomerdesign.com/Cdsa/FR/56FR61372.pdf |url-status=live |archive-url=https://ghostarchive.org/archive/20221228191210/https://isomerdesign.com/Cdsa/FR/56FR61372.pdf |archive-date=28 December 2022 |access-date=9 July 2022 |website=Isomer Design |publisher=[[Drug Enforcement Administration]] }}</ref> The substance has remained unregulated under the Controlled Substances Act in the United States ever since. Furthermore, pursuant to [[DEA]] regulations, certain Benzedrex inhalers are specifically exempt from the Controlled Substances Act.<ref>{{Cite web |title=Sec. 1308.22 Excluded substances. |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1308.22 |archive-url=https://archive.today/20230531045652/https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1308.22 |archive-date=May 31, 2023 |access-date=May 30, 2023 |website=Code of Federal Regulations |publisher=[[Drug Enforcement Administration]]}}</ref><ref>{{Cite web | vauthors = Haislip G |date=January 11, 1989 |title=Excluded Non-narcotic Over-the-counter Substances |url=https://archives.federalregister.gov/issue_slice/1989/1/19/2099-2101.pdf#page=2 |archive-url=https://web.archive.org/web/20230627005235/https://archives.federalregister.gov/issue_slice/1989/1/19/2099-2101.pdf |archive-date=June 27, 2023 |access-date=June 26, 2023 |website=[[Federal Register]] |publisher=[[Drug Enforcement Administration]] }}</ref> Propylhexedrine remains regulated under the laws of several U.S. states. These states include the states of Alaska,<ref>{{Cite web |title=2014 Alaska Statutes :: Title 11 - Criminal Law :: Chapter 11.71 - Controlled Substances :: Article 02 - Standards and Schedules :: Sec. 11.71.180 Schedule VA. |url=https://law.justia.com/codes/alaska/2014/title-11/chapter-11.71/article-02/section-11.71.180 |archive-url=https://archive.today/20231222072102/https://law.justia.com/codes/alaska/2014/title-11/chapter-11.71/article-02/section-11.71.180 |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref> Arizona,<ref>{{Cite web |title=2005 Arizona Revised Statutes - :: Revised Statutes §13-3401 Definitions |url=https://law.justia.com/codes/arizona/2005/title13/03401.html |archive-url=https://archive.today/20231222072833/https://law.justia.com/codes/arizona/2005/title13/03401.html |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref> Florida,<ref>{{Cite web |title=2011 Florida Statutes :: TITLE XLVI — CRIMES :: Chapter 893 — Drug Abuse Prevention and Control :: 893.03 — Standards and schedules. |url=https://law.justia.com/codes/florida/2011/titlexlvi/chapter893/section893.03 |archive-url=https://archive.today/20231222073123/https://law.justia.com/codes/florida/2011/titlexlvi/chapter893/section893.03 |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref> Georgia,<ref>{{Cite web |title=2022 Georgia Code :: Title 16 - Crimes and Offenses :: Chapter 13 - Controlled Substances :: Article 2 - Regulation of Controlled Substances :: Part 1 - Schedules, Offenses, and Penalties :: § 16-13-29.1. Nonnarcotic Substances Excluded From Schedules of Controlled Substances |url=https://law.justia.com/codes/georgia/2022/title-16/chapter-13/article-2/part-1/section-16-13-29-1/ |archive-url=https://archive.today/20231222073402/https://law.justia.com/codes/georgia/2022/title-16/chapter-13/article-2/part-1/section-16-13-29-1/ |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref> Idaho,<ref>{{Cite web |title=2010 Idaho Code :: Title 37 Food, Drugs, and Oil :: Chapter 27 Uniform Controlled Substances :: Article Ii :: 37-2713 Schedule V. |url=https://law.justia.com/codes/idaho/2010/title37/t37ch27sect37-2713.html |archive-url=https://archive.today/20231222073801/https://law.justia.com/codes/idaho/2010/title37/t37ch27sect37-2713.html |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref> Kansas,<ref>{{Cite web |title=2017 Kansas Statutes :: Chapter 65 Public Health :: Article 41 Controlled Substances :: 65-4113 Substances included in schedule V. |url=https://law.justia.com/codes/kansas/2021/chapter-65/article-41/section-65-4113/ |archive-url=https://archive.today/20231222074029/https://law.justia.com/codes/kansas/2017/chapter-65/article-41/section-65-4113/ |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref> and Rhode Island.<ref>{{Cite web |title=2021 Rhode Island General Laws :: Title 21 - Food and Drugs :: Chapter 21-28 - Uniform Controlled Substances Act :: Section 21-28-2.08 - Contents of schedules. |url=https://law.justia.com/codes/rhode-island/2021/title-21/chapter-21-28/section-21-28-2-08/ |archive-url=https://archive.today/20231222074400/https://law.justia.com/codes/rhode-island/2021/title-21/chapter-21-28/section-21-28-2-08/ |archive-date=2023-12-22 |access-date=2023-12-22 |website=Justia Law |language=en}}</ref>

===Recreational use===
Multiple public health agencies (most notably within the United States) have warned against the recreational use of propylhexedrine and advised for its use only as directed by a product's labeling; nonetheless it has been reported, through the literature as early as 1959, that propylhexedrine products have been used for recreational purposes.<ref name="Rose_1959">{{Cite journal | vauthors = Rose W |date=September 1959 |title=Arzneimittelsucht durch Mißbrauch von sogenannten Appetitzüglern (Obesin) |journal=Archiv für Toxikologie |language=de |volume=17 |issue=5 |pages=331–335 |doi=10.1007/BF00577633 |bibcode=1959ArTox..17..331R |issn=1432-0738 |s2cid=31539217}}</ref> Recreational use is potentially fatal, its risks are magnified when administering the substance through injection means, and the adverse effects of recreational propylhexedrine are more severe when compared to related substances.<ref name="Fornazzari">{{cite journal | vauthors = Fornazzari L, Carlen PL, Kapur BM | title = Intravenous abuse of propylhexedrine (Benzedrex) and the risk of brainstem dysfunction in young adults | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 13 | issue = 4 | pages = 337–339 | date = November 1986 | pmid = 2877725 | doi = 10.1017/S0317167100036696 | doi-access = free }}</ref><ref name="toxicity-death">{{cite journal | vauthors = Holler JM, Vorce SP, McDonough-Bender PC, Magluilo J, Solomon CJ, Levine B | title = A drug toxicity death involving propylhexedrine and mitragynine | journal = Journal of Analytical Toxicology | volume = 35 | issue = 1 | pages = 54–59 | date = January 2011 | pmid = 21219704 | doi = 10.1093/anatox/35.1.54 | doi-access = free }}</ref> The undesirable side effects of propylhexedrine at recreational doses are less tolerable compared to other substances that produce similar effects; consequently, propylhexedrine is less desirable for recreational use.<ref name="National Capital Poison Control">{{Cite web |title=Propylhexedrine (Benzedrex) |url=https://www.poison.org/articles/propylhexedrine |url-status=dead |archive-url=https://ghostarchive.org/archive/20230716060703/https://www.poison.org/articles/propylhexedrine |archive-date=16 July 2023 |access-date=2023-07-16 |website=National Capital Poison Control |language=en }}</ref><ref name="Anderson_1970">{{cite journal | vauthors = Anderson ED | title = Propylhexedrine (Benzedrex) psychosis | journal = The New Zealand Medical Journal | volume = 71 | issue = 456 | pages = 302 | date = May 1970 | pmid = 5270979 | s2cid = 30786926 }}</ref><ref name="Sturner_1974">{{cite journal | vauthors = Sturner WQ, Spruill FG, Garriott JC | title = Two propylhexedrine-associated fatalities: Benzedrine revisited | journal = Journal of Forensic Sciences | volume = 19 | issue = 3 | pages = 572–574 | date = July 1974 | pmid = 4137337 | doi = 10.1520/JFS10213J }}</ref> The fact that propylhexedrine is less potent than comparable substances has also limited recreational use.<ref>{{Cite web | vauthors = Cooper D |title="Future Synthetic Drugs of Abuse" |url=https://www.erowid.org/library/books_online/future_synthetic/ |archive-url=https://web.archive.org/web/20230809071331/https://www.erowid.org/library/books_online/future_synthetic/ |archive-date=August 9, 2023 |access-date=2023-08-09 |website=[[Erowid]] |publisher=[[Drug Enforcement Administration]] }}</ref><ref>{{cite journal | vauthors = Garriott JC | title = Editorial: Propylhexadrine - a new dangerous drug? | journal = Clinical Toxicology | volume = 8 | issue = 6 | pages = 665–666 | date = 1975 | pmid = 6189 | doi = 10.3109/15563657508990092 }}</ref> Even in areas with prevalent substance use, the use of propylhexedrine was reported as non-significant.<ref name="Smith_1988">{{cite journal | vauthors = Smith DE, Wesson DR, Sees KL, Morgan JP | title = An epidemiological and clinical analysis of propylhexedrine abuse in the United States | journal = Journal of Psychoactive Drugs | volume = 20 | issue = 4 | pages = 441–442 | date = 1988-10-01 | pmid = 2907528 | doi = 10.1080/02791072.1988.10472514 }}</ref> The recreational use of nasal decongestant,<ref name="Anderson_1970" /><ref>{{Cite news | vauthors = Curry B |date=September 5, 1985 |title=Abuse of Potentially Fatal Nasal Inhaler Medication by Injection Called Widespread |newspaper=[[LA Times]] |url=https://www.latimes.com/archives/la-xpm-1985-09-05-mn-24755-story.html |access-date=September 7, 2023 |archive-url=https://web.archive.org/web/20210509111800/https://www.latimes.com/archives/la-xpm-1985-09-05-mn-24755-story.html |archive-date=May 9, 2021 }}</ref> anorectic,<ref name="Rose_1959" /> and anticonvulsant preparations<ref>{{cite journal | vauthors = Darcın AE, Dilbaz N, Okay IT | title = Barbexaclone abuse in a cannabis ex-user | journal = Substance Abuse | volume = 31 | issue = 4 | pages = 270–272 | date = October 2010 | pmid = 21038181 | doi = 10.1080/08897077.2010.514246 | s2cid = 7076881 }}</ref> have all been reported. The recreational use of propylhexedrine products has been on the rise since the early 2000s.<ref name="Teja_2020">{{cite journal | vauthors = Teja N, Dodge CP, Stanciu CN | title = Abuse, Toxicology and the Resurgence of Propylhexedrine: A Case Report and Review of Literature | journal = Cureus | volume = 12 | issue = 10 | pages = e10868 | date = October 2020 | pmid = 33178521 | pmc = 7652022 | doi = 10.7759/cureus.10868 | doi-access = free }}</ref>

In 2021, the [[United States Food & Drug Administration]] issued the following warning<ref name="Center for Drug Evaluation and Research_2021" /> in regard to [[Recreational drug use|recreational use]] of propylhexedrine products in manners inconsistent with their labeling:

{{Blockquote|text="...[T]he abuse and misuse of the over-the-counter (OTC) nasal decongestant propylhexedrine can lead to serious harm such as heart and mental health problems. Some of these complications, which include fast or abnormal heart rhythm, high blood pressure, and paranoia, can lead to hospitalization, disability, or death....Propylhexedrine is safe and effective when used as directed."}}

That same year, the [[Indian Health Service]] issued the following statement<ref name="National Pharmacy & Therapeutics Committee_2021">{{Cite web |date=2021 |title=Abuse and Misuse of Propylhexedrine Nasal Decongestant Causes Serious Harm |url=https://www.ihs.gov/nptc/pharmacovigilance/medication-safety-resources-archive/2021/abuse-and-misuse-of-propylhexedrine-nasal-decongestant-causes-serious-harm/ |archive-url=https://web.archive.org/web/20230528203228/https://www.ihs.gov/nptc/pharmacovigilance/medication-safety-resources-archive/2021/abuse-and-misuse-of-propylhexedrine-nasal-decongestant-causes-serious-harm/ |archive-date=May 28, 2023 |access-date=2023-11-03 |website=National Pharmacy & Therapeutics Committee |publisher=[[Indian Health Service]] |language=en}}</ref> in reference to the [[Recreational drug use|recreational use]] of propylhexedrine products:

{{Blockquote|text="Only use propylhexedrine according to the instructions on the package label. Do not use it in ways other than inhalation. Seek medical attention immediately for by calling [emergency services] or [[poison control center|Poison Control]]...for anyone using propylhexedrine who experiences [the following.] [These following  reactions are] [s]evere anxiety or agitation, confusion, hallucinations, or paranoia[,] [r]apid heartbeat or abnormal heart rhythm[,] [or] [c]hest pain or tightness[.]"}}

A year later, in 2022, the [[U.S. Army]] published the following guidance<ref name="Parrish_2022">{{Cite web | vauthors = Parrish A |date=October 26, 2022 |title=FDA issues drug misuse guidance |url=https://www.army.mil/article/261494/fda_issues_drug_misuse_guidance |archive-url=https://web.archive.org/web/20221130001549/https://www.army.mil/article/261494/fda_issues_drug_misuse_guidance |archive-date=November 30, 2022 |access-date=2023-11-13 |website=[[United States Army]] |language=en}}</ref> on propylhexedrine. The guidance states that recreational use of propylhexedrine is not permissible by service-members, can open its participants up to disciplinary action, and carries potentially fatal risks:

{{Blockquote|text="When disciplining a member for suspected use of any drug, it is important to consult [legal counsel] on how to proceed, [according to the Office of Drug Demand Reduction]...This is especially important when the evidence supporting discipline consists of scientific reports and data that may require special assistance in their interpretation. In cases involving [propylhexedrine], legal consultation is highly recommended."}}

Put briefly, the [[Food and Drug Administration|Food & Drug Administration]], [[Indian Health Service]], and [[U.S. Army]] all advise individuals not to use propylhexedrine products for recreational purposes.

=== Economics ===
Propylhexedrine, under the brand name Benzedrex, is sold online by retailers such as [[Amazon (company)|Amazon]], [[eBay]], and [[Walmart]].<ref name="B. F. Ascher and Company">{{Cite web |title=Benzedrex Inhaler |url=https://www.bfascher.com/products/benzedrex/ |url-status=dead |archive-url=https://web.archive.org/web/20230708192205/https://www.bfascher.com/products/benzedrex/ |archive-date=8 July 2023 |access-date=July 8, 2023 |website=B. F. Ascher and Company }}</ref> Propylhexedrine has been sold in some countries as an [[anorectic]] or as part of an anticonvulsant preparation; however, such products are not sold freely to consumers and require a physician's prescription.

=== Brand names ===

==== Benzedrex inhaler ====
[[File:Benzedrex.jpg|thumb|Benzedrex inhaler, {{circa|2023}}, manufactured by B. F. Ascher & Co.]]
Propylhexedrine, as a nasal decongestant, is currently marketed under the trade name Benzedrex. The name Benzedrex was initially trademarked by [[Smith, Kline & French]] in 1944.<ref>{{Cite web |title=Benzedrex Trademark of B.F. Ascher & Company Inc - Registration Number 0896775 - Serial Number 72340742 |url= http://trademarks.justia.com/723/40/benzedrex-72340742.html |url-status=dead |archive-url= https://archive.today/20230716051433/https://trademarks.justia.com/723/40/benzedrex-72340742.html |archive-date=July 16, 2023 |access-date=2023-07-16 |website=Justia |language=en}}</ref> The brand was passed onto Menley James Laboratories (through a subsidiary, NuMark Laboratories) in 1990, and was finally acquired by B. F. Ascher & Co. in 1998.<ref>{{Cite web | vauthors = Robertson V |date=February 17, 2004 |title=Prince v. B.F. Ascher Company, Inc., 90 P.3d 1020 (Okla. Civ. App. 2004) |url=https://casetext.com/case/prince-v-bf-ascher-company-inc |url-status=live |archive-url=https://ghostarchive.org/archive/20230716060731/https://casetext.com/case/prince-v-bf-ascher-company-inc |archive-date=16 July 2023 |access-date=2023-07-16 |website=CaseText }}</ref><ref>{{Cite web |date=March 1, 1999 |title=B.F. Ascher marks 50th year. |url= https://www.thefreelibrary.com/B.F.+Ascher+marks+50th+year.-a054082926 |archive-url= https://archive.today/20230809072522/https://www.thefreelibrary.com/B.F.+Ascher+marks+50th+year.-a054082926 |archive-date=August 9, 2023 |access-date=2023-08-09 |website=The Free Library |publisher=Chain Drug Review}}</ref>

==== Dristan inhaler ====
[[File:Dristan_Inhaler.jpg|thumb|upright|Dristan-brand inhaler, {{circa|1966}} manufactured by [[Whitehall Laboratories]] ]]
Propylhexedrine was also sold in inhaler form by [[Whitehall Laboratories]] (Wyeth) under the [[Dristan]] brand name as an inhaler.<ref>{{Cite web |date=November 24, 1989 |title=Action in Respect of International Conventions on Narcotic Drugs and Psychotropic Substances |url=https://iris.who.int/bitstream/handle/10665/163484/EB85_23_eng.pdf?sequence=1 |archive-url=https://web.archive.org/web/20231029070234/https://iris.who.int/bitstream/handle/10665/163484/EB85_23_eng.pdf?sequence=1 |archive-date=October 29, 2023 |access-date=October 29, 2023 |website=[[World Health Organization]] }}</ref> In January 1966, propylhexedrine replaced [[mephentermine]] as the active ingredient in the product.<ref>{{cite journal | vauthors = Angrist BM, Schweitzer JW, Gershon S, Friedhoff AJ | title = Mephentermine psychosis: misuse of the Wyamine inhaler | journal = The American Journal of Psychiatry | volume = 126 | issue = 9 | pages = 1315–1317 | date = March 1970 | pmid = 5413209 | doi = 10.1176/ajp.126.9.1315 }}</ref> The Dristan inhaler has since been discontinued. Furthermore, Wyeth was acquired by [[Pfizer]] in 2009. All products currently sold under the [[Dristan]] brand are manufactured by Foundation Consumer Brands; Foundation Consumer Brands acquired the Dristan brand in 2020.<ref>{{Cite web |date=October 1, 2020 |title=Foundation Consumer Healthcare to Add Seven Over-the-Counter Brands to Expanding Portfolio of Healthcare Products |url=https://foundationch.com/assets/press-release/2020-10-01.pdf |archive-url=https://web.archive.org/web/20231113224757/https://foundationch.com/assets/press-release/2020-10-01.pdf |archive-date=November 13, 2023 |access-date=November 13, 2023 |website=Foundation Consumer Brands |publisher=[[Kelso & Company]]}}</ref> Foundation Consumer Brands is itself owned by [[Kelso & Company]].

==== Obesin ====
[[File:Obesin.jpg|thumb|left|Obesin pill-case, {{circa|1974}} manufactured by Fahlberg-List]]
Propylhexedrine has also seen use in [[Europe]] as an [[appetite suppressant]], under the trade name Obesin.<ref name="pmid2874970">{{cite journal | vauthors = Wesson DR | title = Propylhexdrine | journal = Drug and Alcohol Dependence | volume = 17 | issue = 2–3 | pages = 273–278 | date = June 1986 | pmid = 2874970 | doi = 10.1016/0376-8716(86)90013-X }}</ref> Obesin has been referenced in literature dating back to the 1950s.<ref name="Polster_1965">{{cite journal | vauthors = Polster H | title = Über eine Vergiftung mit dem Appetitzügler Propylhexedrin "Obesin", bei einem 3 Ährigen Kinde | trans-title = About poisoning with the appetite suppressant propylhexedrine "Obesin" in a 3-year-old child | language = de | journal = Archiv für Toxikologie | volume = 20 | pages = 271–273 | date = February 1965 | issue = 5 | pmid = 14272412 | doi = 10.1007/BF00577551 | s2cid = 19812917 }}</ref><ref name="Rose_1959" /> Obesin was manufactured by Fahlberg-List in [[East Germany]] from 1958 to around 1976. The discontinuation of Obesin was the result of increased regulatory restrictions on [[Over-the-counter drug|over-the-counter]] [[anorectic]]s. These restrictions began to be imposed in 1974.<ref name="Winter_1976">{{Cite journal | vauthors = Winter E |date=1976 |title=Bemerkungen zu Drogenmißbrauch und -abhängigkeit vom Amphetamin- Typ unter besonderer Berücksichtigung des Amphetaminils (Aponeuron (R) ) |trans-title=Comments on amphetamine-type drug abuse and dependence with special reference to amphetaminil (Aponeuron) |url=https://www.jstor.org/stable/45253962 |journal=Psychiatrie, Neurologie und medizinische Psychologie |language=DE |volume=28 |issue=9 |pages=513–525 |jstor=45253962 |issn=0033-2739}}</ref> Fahlberg-List itself dissolved in 1995.

==== Maliasin ====
[[File:Maliasin.jpg|thumb|left|Maliasin ([[Barbexaclone]]) carton, {{circa|2002}} manufactured by [[Knoll Pharmaceuticals]]]]
Propylhexedrine is a component in the [[anticonvulsant]] preparation [[barbexaclone]]. Its ''S''-isomer ([[levopropylhexedrine]] or <small>L</small>-propylhexedrine) is bonded with [[phenobarbital]] for the purpose of offsetting the [[barbiturate]]-induced [[sedation]].<ref name="pmid2874970" /> Barbexaclone has been known under the brand name of Maliasin, manufactured by [[Abbott Laboratories]], as early as 1965.<ref>{{cite journal | vauthors = Krueger HJ, Schwarz H | title = [Clinical Communication on the Therapy of Epilepsy With Maliasin] | journal = Die Medizinische Welt | volume = 14 | pages = 690–692 | date = April 1965 | pmid = 14276849 }}</ref><ref>{{Cite web |title=MALIASIN Trademark - Registration Number 0797076 - Serial Number 72213021 |url=http://trademarks.justia.com/722/13/maliasin-72213021.html |url-status=dead |archive-url=https://web.archive.org/web/20230716060838/https://trademarks.justia.com/722/13/maliasin-72213021.html |archive-date=16 July 2023 |access-date=2023-07-16 |website=Justia |language=en }}</ref> Maliasin has also been manufactured by [[Knoll Pharmaceuticals]]; Knoll is a company acquired by [[Abbott Laboratories]]. In 2010, Abbott discontinued sale of its barbexaclone preparation in many countries.<ref>{{Cite web | vauthors = Serracchiani D |date=January 31, 2011 |title=Parliamentary question {{!}} Maliasin {{!}} P-001035/2011 {{!}} European Parliament |url=https://www.europarl.europa.eu/doceo/document/P-7-2011-001035_EN.html |url-status=dead |archive-url=https://ghostarchive.org/archive/20230716050714/https://www.europarl.europa.eu/doceo/document/P-7-2011-001035_EN.html |archive-date=16 July 2023 |access-date=2023-07-16 |website=[[European Parliament]] |language=en }}</ref>

==== Eventin ====
Levopropylhexedrine (the more active optical isomer of propylhexedrine) has been used as an [[anorectic|appetite suppressant]] under the brand name Eventin. Eventin's use has been documented as early as 1958.<ref>{{cite journal | vauthors = Hofer R, Locker A | title = [Therapeutic experiences with the appetite depressant eventin] | journal = Wiener Medizinische Wochenschrift | volume = 108 | issue = 14 | pages = 304–306 | date = April 1958 | pmid = 13558159 | url = https://pubmed.ncbi.nlm.nih.gov/13558159/ }}</ref>

== References ==
{{reflist}}

{{Decongestants}}
{{Stimulants}}
{{Monoamine releasing agents}}
{{TAAR ligands}}

[[Category:Anorectics]]
[[Category:Cyclohexyl compounds]]
[[Category:Decongestants]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Sympathomimetics]]
[[Category:TAAR1 agonists]]
[[Category:Vasoconstrictors]]
[[Category:VMAT inhibitors]]