Zimelidine
SSRI antidepressant drug
- N06AB02 (WHO)
- Withdrawn worldwide
19.4±3.6 hours (norzimelidine)[1]
- (Z)-3-(4-Bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine
- 56775-88-3
N 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
- 5365247
- DB04832
Y
- 4517305 Y
- 3J928617DW
- ChEMBL37744 Y
- DTXSID6048462
- Interactive image
- Brc2ccc(C(=C/CN(C)C)/c1cccnc1)cc2
InChI
- InChI=1S/C16H17BrN2/c1-19(2)11-9-16(14-4-3-10-18-12-14)13-5-7-15(17)8-6-13/h3-10,12H,11H2,1-2H3/b16-9-Y
- Key:OYPPVKRFBIWMSX-SXGWCWSVSA-NY
N
Y (what is this?) (verify)Zimelidine (INN, BAN) (brand names Zimeldine, Normud, Zelmid) was one of the first selective serotonin reuptake inhibitor (SSRI) antidepressants to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants.[2]
Zimelidine was developed in the late 1970s and early 1980s by Arvid Carlsson, who was then working for the Swedish company Astra AB. It was discovered following a search for drugs with structures similar to brompheniramine (it is a derivative of brompheniramine), an antihistamine with antidepressant activity. Zimelidine was first sold in 1982.[3]
While zimelidine had a very favorable safety profile, within a year and a half of its introduction, rare case reports of Guillain–Barré syndrome emerged that appeared to be caused by the drug, prompting its manufacturer to withdraw it from the market.[3][4] After its withdrawal, it was succeeded by fluvoxamine and fluoxetine (derived from the antihistamine diphenhydramine) in that order, and the other SSRIs.
Mechanism of action
The mode of action is a strong reuptake inhibition of serotonin from the synaptic cleft. Postsynaptic receptors are not acted upon.
Other uses
Zimelidine was reported by Montplaisir and Godbout to be very effective for cataplexy in 1986, back when this was usually controlled by tricyclic antidepressants, which often had anticholinergic effects.[5] Zimelidine was able to improve cataplexy without causing daytime sleepiness.[5]
Side effects
Most often reported were:
- Dry mouth, dryness of pharyngeal and nasal membranes
- Increased sweating (hyperhidrosis)
- Vertigo
- Nausea
Interactions
- MAO inhibitors — severe or life-threatening reactions possible[medical citation needed]
See also
References
- ^ Caillé G, Kouassi E, de Montigny C (1986). "Pharmacokinetic study of zimelidine using a new GLC method". Clinical Pharmacokinetics. 8 (6): 530–40. doi:10.2165/00003088-198308060-00004. PMID 6228368. S2CID 42052631.
- ^ Barondes, Samuel H. (2005-01-26). Better than Prozac: Creating the Next Generation of Psychiatric Drugs. Oxford University Press. pp. 39–40. ISBN 978-0-19-517979-8.
- ^ a b Fagius J, Osterman PO, Sidén A, Wiholm BE (January 1985). "Guillain-Barré syndrome following zimeldine treatment". Journal of Neurology, Neurosurgery, and Psychiatry. 48 (1): 65–9. doi:10.1136/jnnp.48.1.65. PMC 1028185. PMID 3156214.
- ^ Carlsson A (November 2001). "A paradigm shift in brain research". Science. 294 (5544): 1021–4. Bibcode:2001Sci...294.1021C. doi:10.1126/science.1066969. PMID 11691978. S2CID 24365669.
- ^ a b Godbout R, Montplaisir J (1986). "The effect of zimelidine, a serotonin-reuptake blocker, on cataplexy and daytime sleepiness of narcoleptic patients". Clinical Neuropharmacology. 9 (1): 46–51. doi:10.1097/00002826-198602000-00004. PMID 2950994.
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Specific reuptake inhibitors and/or receptor modulators | |||||||||||||||||
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
