Zimelidine
Clinical data
Trade namesZelmid
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • Withdrawn worldwide
Pharmacokinetic data
Elimination half-life8.4±2 hours (parent compound)
19.4±3.6 hours (norzimelidine)[1]
Identifiers
  • (Z)-3-(4-Bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine
CAS Number
  • 56775-88-3 ☒N 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H17BrN2
Molar mass317.230 g·mol−1
3D model (JSmol)
  • Brc2ccc(C(=C/CN(C)C)/c1cccnc1)cc2
  • 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- checkY
  • Key:OYPPVKRFBIWMSX-SXGWCWSVSA-N checkY
 ☒NcheckY (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:

Interactions

See also

References

  1. ^ 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.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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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