Dimetindene

Dimetindene
Clinical data
Trade names	Fenistil
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral, topical
ATC code	D04AA13 (WHO) R06AB03 (WHO);
Legal status
Legal status	AU: S4 (Prescription only); UK: General sales list (GSL, OTC);
Identifiers
	IUPAC name N,N-Dimethyl-2-[3-(1-pyridin-2-ylethyl)-1H-inden-2-yl]ethan-1-amine;
CAS Number	5636-83-9 3614-69-5;
PubChem CID	21855;
DrugBank	DB08801 ;
ChemSpider	20541 ;
UNII	661FH77Z3P;
KEGG	D07853 ;
ChEMBL	ChEMBL22108 ;
CompTox Dashboard (EPA)	DTXSID9022942 ;
ECHA InfoCard	100.024.622
Chemical and physical data
Formula	C20H24N2
Molar mass	292.426 g·mol−1
3D model (JSmol)	Interactive image;
Chirality	Racemic mixture
	SMILES n1ccccc1C(C=3c2ccccc2CC=3CCN(C)C)C;
	InChI InChI=1S/C20H24N2/c1-15(19-10-6-7-12-21-19)20-17(11-13-22(2)3)14-16-8-4-5-9-18(16)20/h4-10,12,15H,11,13-14H2,1-3H3 ; Key:MVMQESMQSYOVGV-UHFFFAOYSA-N ;
	(verify)

Dimetindene , also sold under the brand name Fenistil, is an antihistamine/anticholinergic. It is a first generation^[1] selective H1 antagonist.^[2] Dimetindene is an atypical first generation H1 antagonist as it only minimally^[3] passes across the blood-brain barrier.

Dimetindene is also an M2 receptor antagonist.^[4]

It was patented in 1958 and came into medical use in 1960.^[5]

Medical use

Dimetindene is used orally and topically as an antipruritic.^[6] It is used topically to treat skin irritations, such as insect bites. Dimetindene is also administered orally to treat allergies, such as hay fever.

It is commonly formulated as its maleic acid salt, dimethindene maleate.

Names

It is sold under the brand name Fenistil among others.

Synthesis

Note that Dolispan Fb: [1613-24-7] shares various of the first steps of the synthesis, indicating that 5 might already be pharmaceutically active in its own right.

The base catalyzed alkylation between Diethyl Benzylmalonate [607-81-8] (1) and 2-Chloroethyldimethylamine [107-99-3] (2) gives Diethyl 2-benzyl-2-(2-(dimethylamino)ethyl)malonate [1805-03-4] (3). Saponification of both esters gives 2-Benzyl-2-(2-(Dimethylamino)Ethyl)Malonic Acid [92501-97-8] (4). Decarboxylation of one of the acids leads to 2-Benzyl-4-(Dimethylamino)Butanoic Acid [1613-23-6] (5). A Haworth type intramolecular Friedel-Crafts acylation leads to 2-[2-(Dimethylamino)ethyl]-1-indanone [3409-21-0] (6). Base catalyzed alkylation of the carbonyl group with 2-Ethylpyridine [100-71-0] (7) gives CID:12963073 (8). Lastly, dehydration of the alcohol completes the synthesis of Dimethindene (9).

References

^ Fromer LM, Ortiz GR, Dowdee AM (September 2008). "Assessment of Patient Attitudes About Mometasone Furoate Nasal Spray: The Ease-of-Use Patient Survey". The World Allergy Organization Journal. 1 (9): 156–9. doi:10.1186/1939-4551-1-9-145. PMC 3651039. PMID 23282579.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ "Dimetindene". Drugs.com.
^ Noguchi; Inukai; Kuno; Tanaka (June 1992). "The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking". Physiol. Behav. 51 (6): 1123–1127. doi:10.1016/0031-9384(92)90297-f. PMID 1353628. S2CID 29562845.
^ Matsumoto Y, Miyazato M, Furuta A, Torimoto K, Hirao Y, Chancellor MB, Yoshimura N (April 2010). "Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of bladder afferent activity in rats". Urology. 75 (4): 862–7. doi:10.1016/j.urology.2009.12.013. PMC 2871158. PMID 20156651.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN 9783527607495.
^ Wexler L (June 1962). "A clinical evaluation of dimethindene". Current Therapeutic Research, Clinical and Experimental. 4: 306–9. PMID 14006402.
^ Huebner, C. F., Donoghue, E., Wenk, P., Sury, E., Nelson, J. A. (April 1960). "A NEW CLASS OF HIGHLY ACTIVE ANTIHISTAMINICS". Journal of the American Chemical Society. 82 (8): 2077–2078. doi:10.1021/ja01493a060. ISSN 1520-5126 0002-7863, 1520-5126. {{cite journal}}: Check |issn= value (help)
^ Charles Ferdinand Huebner, U.S. patent 2,947,756 (1960 to Ciba).
^ Huebner Charles Ferdinand, U.S. patent 2,970,149 (1961 to CIBA PHARM PROD Inc).
^ Huebner Charles Ferdinand, U.S. patent 3,060,186 (1962 to Ciba Geigy Corp).

[1] Fromer LM, Ortiz GR, Dowdee AM (September 2008). "Assessment of Patient Attitudes About Mometasone Furoate Nasal Spray: The Ease-of-Use Patient Survey". The World Allergy Organization Journal. 1 (9): 156–9. doi:10.1186/1939-4551-1-9-145. PMC 3651039. PMID 23282579.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[2] "Dimetindene". Drugs.com.

[3] Noguchi; Inukai; Kuno; Tanaka (June 1992). "The suppression of olfactory bulbectomy-induced muricide by antidepressants and antihistamines via histamine H1 receptor blocking". Physiol. Behav. 51 (6): 1123–1127. doi:10.1016/0031-9384(92)90297-f. PMID 1353628. S2CID 29562845.

[4] Matsumoto Y, Miyazato M, Furuta A, Torimoto K, Hirao Y, Chancellor MB, Yoshimura N (April 2010). "Differential roles of M2 and M3 muscarinic receptor subtypes in modulation of bladder afferent activity in rats". Urology. 75 (4): 862–7. doi:10.1016/j.urology.2009.12.013. PMC 2871158. PMID 20156651.

[Fis2006-5] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 547. ISBN 9783527607495.

[6] Wexler L (June 1962). "A clinical evaluation of dimethindene". Current Therapeutic Research, Clinical and Experimental. 4: 306–9. PMID 14006402.

[7] Huebner, C. F., Donoghue, E., Wenk, P., Sury, E., Nelson, J. A. (April 1960). "A NEW CLASS OF HIGHLY ACTIVE ANTIHISTAMINICS". Journal of the American Chemical Society. 82 (8): 2077–2078. doi:10.1021/ja01493a060. ISSN 1520-5126 0002-7863, 1520-5126. {{cite journal}}: Check |issn= value (help)

[8] Charles Ferdinand Huebner, U.S. patent 2,947,756 (1960 to Ciba).

[9] Huebner Charles Ferdinand, U.S. patent 2,970,149 (1961 to CIBA PHARM PROD Inc).

[10] Huebner Charles Ferdinand, U.S. patent 3,060,186 (1962 to Ciba Geigy Corp).

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v t e Antipruritics (D04)
Antihistamines for topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Isothipendyl Mepyramine Pheniramine Promethazine Thenalidine Thonzylamine Tolpropamine Tripelennamine
Anesthetics for topical use	Benzocaine Cinchocaine Dibucaine Lidocaine Oxybuprocaine Pramocaine Quinisocaine Tetracaine
Others	Corticosteroids (e.g., hydrocortisone) Counterirritants (e.g., mint oil, menthol, camphor) Difelikefalin Doxepin Nalfurafine

v t e Antihistamines (R06)
Benzimidazoles (*)	Astemizole Azelastine Bilastine Emedastine Mizolastine Talastine
Diarylmethanes	Diarylmethoxyalkylamines: Bromazine (bromodiphenhydramine) Carbinoxamine Chlorphenoxamine Clemastine Diphenhydramine (+naproxen) Diphenylpyraline Doxylamine Ebastine Orphenadrine Diphenylmethanolpiperidines: Fexofenadine Terfenadine Diphenylmethylpiperazines: Buclizine Cetirizine Levocetirizine Chlorcyclizine Cinnarizine Cyclizine Etodroxizine Hydroxyzine Meclizine Oxatomide Phenylpyridinylpropanamines: Brompheniramine Chlorphenamine Dexbrompheniramine (+pseudoephedrine) Dexchlorpheniramine (+betamethasone) Pheniramine Others: Acrivastine Bamipine Dimetindene Phenyltoloxamine Pyrrobutamine Quifenadine Triprolidine
Ethylenediamines	Antazoline Chloropyramine Histapyrrodine Mepyramine (pyrilamine) Methapyrilene Phenbenzamine Thenalidine Tripelennamine (pyribenzamine)
Tricyclics	Dibenzocycloheptenes: Antidepressants (e.g., amitriptyline) Azatadine Cyproheptadine Deptropine Desloratadine Ketotifen Loratadine Rupatadine Phenothiazines: Alimemazine Fenethazine Hydroxyethylpromethazine Isothipendyl Mequitazine Methdilazine Oxomemazine Promethazine Others: Antidepressants (e.g., doxepin, mirtazapine, trimipramine) Epinastine Latrepirdine Mebhydrolin Olopatadine Perlapine Phenindamine Pimethixene
Others	Phenylpiperazines: Antidepressants (e.g., trazodone) Phenbenzamine
For topical use	Bamipine Chloropyramine Chlorphenoxamine Clemastine Dimetindene Diphenhydramine Doxepin Isothipendyl Mepyramine (pyrilamine) Promethazine