Pentazocine

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Pentazocine
Pentazocine-racemate2DCSD.svg
(R)-pentazocine3DanJ.gif (S)-pentazocine3DanJ.gif
Systematic (IUPAC) name
(2RS,6RS,11RS)-6,11-dimethyl-3-(3-methylbut-2-en-1-yl)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-8-ol
or
2-dimethylallyl-5,9-dimethyl-2'-hydroxybenzomorphan
Clinical data
Pregnancy cat.
Legal status
Routes Oral, IV, IM
Pharmacokinetic data
Bioavailability ~20% orally
Metabolism Hepatic
Half-life 2 to 3 hours
Excretion Renal
Identifiers
CAS number 359-83-1 YesY
ATC code N02AD01
PubChem CID 441278
IUPHAR ligand 1606
DrugBank DB00652
ChemSpider 390041 YesY
UNII RP4A60D26L YesY
KEGG D00498 YesY
ChEMBL CHEMBL560 YesY
Chemical data
Formula C19H27NO 
Mol. mass 285.424 g/mol
 YesY (what is this?)  (verify)

Pentazocine is a synthetically-prepared prototypical mixed agonist–antagonist narcotic (opioid analgesic) drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain. Pentazocine is sold under several brand names, such as Fortral, Sosegon, Talwin NX (with the μ-antagonist naloxone, will cause withdrawal in opioid dependent persons on injection), Talwin, Talwin PX (without naloxone), Fortwin (Lactate injectable form) and Talacen (with acetaminophen). This compound may exist as one of two enantiomers, named (+)-pentazocine and (-)-pentazocine. (-)-pentazocine is a κ-opioid receptor agonist, while (+)-pentazocine is not, instead displaying a ten-fold greater affinity for the σ receptor. Usually, in its oral formulations, it is combined with naloxone so as to prevent people from crushing the tablets, dissolving them in a solvent (like water) and injecting them for a high (as naloxone is not orally bioavailable it produces no effect when the formulation is used orally, but it blocks the opioid effects of pentazocine if injected intravenously for a high).[1] Related drugs include phenazocine, dezocine, cyclazocine and several chemicals used in research on the central nervous system.

Therapeutic uses[edit]

Pentazocine is used primarily to treat pain, although its analgesic effects are subject to a ceiling effect.[2] It has been discontinued by its corporate sponsor in Australia, although it may be available through the special access scheme.[1]

Adverse effects[edit]

Pentazocine.jpg

Side effects are similar to those of morphine, but pentazocine, due to its action at the kappa opioid receptor is more likely to invoke psychotomimetic effects.[2] High dose may cause high blood pressure or high heart rate.[1] It may also increase cardiac work after myocardial infarction when given intravenously and hence this use should be avoided where possible.[1] Respiratory depression is a common side effect, but is subject to a ceiling effect, such that at a certain dose the degree of respiratory depression will no longer increase with dose increases.[1] Likewise rarely it has been associated with agranulocytosis, erythema multiforme and toxic epidermal necrolysis.[1]

Tissue damage at injection sites[edit]

Severe injection site necrosis and sepsis has occurred (sometime requiring amputation of limb) with multiple injection of pentazocine lactate. In addition, animal studies have demonstrated that Pentazocine is tolerated less well subcutaneously than intramuscularly.[3]

Illicit use[edit]

In the 1970s, recreational drug users discovered that combining pentazocine with tripelennamine (a first-generation ethylenediamine antihistamine most commonly dispensed under the brand names Pelamine and Pyribenzamine) produced a euphoric sensation. Since tripelennamine tablets are typically blue in color and brand-name Pentazocine is known as Talwin (hence "Ts"), the pentazocine/tripelennamine combination acquired the slang name Ts and blues. After health-care professionals and drug-enforcement officials became aware of this scenario, the mu-opioid-antagonist naloxone was added to oral preparations containing pentazocine to prevent injection misuse,[4] and the reported incidence of its misuse has declined precipitously since.

Legal status[edit]

Pentazocine was originally classified in Schedule V under the Controlled Substances Act but a petition was filed with the D.E.A. on October 1, 1971, to shift it to Schedule III. The petition was filed by Joseph L. Fink III, a pharmacist and law student at Georgetown University Law Center as part of the course Lawyering in the Public Interest. That petition was accepted for review on November 10, 1971[5] D.E.A. published a Final Rule transferring it to schedule IV on January 10, 1979, with an effective date of February 9, 1979[6] This is understood to be the first instance of a successful petition to reclassify a substance under the relatively recently enacted Controlled Substances Act. Pentazocine is still classified in Schedule IV under the Controlled Substances Act in the United States, even with the addition of Naloxone. although some states classify it in Schedule III. Internationally, pentazocine is a Schedule III drug under the Convention on Psychotropic Substances.[7] Pentazocine has a DEA ACSCN of 9720; being a Schedule IV substance, the DEA does not assign an annual manufacturing quota for pentazocine for the United States.

History[edit]

Pentazocine was developed by the Sterling Drug Company, Sterling-Winthrop Research Institute, of Rensselaer, New York. It was approved by the Food and Drug Administration in June 1967 after being favorably reviewed following testing on 12,000 patients in the United States. The analgesic compound was first made at Sterling in 1958. U.S. testing was conducted between 1961 - 1967. By mid 1967 Pentazocine was already being sold in Mexico, England, and Argentina, under different trade names.[8]

Synthesis[edit]

Pentazocine synthesis: BE 611000  [9]

Pentazocine is synthesized starting from 3,4-dimethylpyridine. It undergoes a reaction with methyl iodide to give 1,3,4-trimethyl pyridinium iodide, which is reacted with 4-methoxybenzylmagnesium chloride. The double bond on C5 of the resulting compound is hydrogenated using a palladium catalyst. The resulting product is O-desmethylated with hydrogen bromide and N-demethylated with cyanogen bromide (Von Braun reaction). Alkylation of the resulting product by 1-bromo-3-methyl-2-butene gives pentazocine.

References[edit]

  1. ^ a b c d e f Sweetman, S, ed. (13 December 2013). "Pentazocine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 17 March 2014. 
  2. ^ a b Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.  edit
  3. ^ "TALWIN (pentazocine lactate) injection, solution". DailyMed. National Institute of Health. Retrieved 2011-12-10. 
  4. ^ "Pentazocine and Naloxone tablets". DailyMed. National Institute of Health. Retrieved 2011-12-10. 
  5. ^ 36 Fed.Reg. 217
  6. ^ 44 Fed. Reg. 2169
  7. ^ "List of psychotropic substances under international control". Green List - Annex to the annual statistical report on psychotropic substances (form P) (23rd ed.). International Narcotics Control Board. August 2003. 
  8. ^ Pain-Killing Drug Approved By F.D.A., New York Times, June 27, 1967, pg. 41.
  9. ^ doi:10.1021/jm00332a001
    This citation will be automatically completed in the next few minutes. You can jump the queue or expand by hand

External links[edit]