Zimelidine
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| Trade names | Zelmid |
| Routes of administration | Oral |
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| Pharmacokinetic data | |
| Elimination half-life | 8.4±2 hours (parent compound) 19.4±3.6 hours (norzimelidine)[1] |
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| Chemical and physical data | |
| Formula | C16H17BrN2 |
| Molar mass | 317.230 g·mol−1 |
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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
[edit]The mode of action is a strong reuptake inhibition of serotonin from the synaptic cleft. Postsynaptic receptors are not acted upon.
Other uses
[edit]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
[edit]Most often reported were:
- Dry mouth, dryness of pharyngeal and nasal membranes
- Increased sweating (hyperhidrosis)
- Vertigo
- Nausea
Interactions
[edit]- MAO inhibitors — severe or life-threatening reactions possible[medical citation needed]
See also
[edit]References
[edit]- ^ 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.