Zimelidine

Last updated
Zimelidine
Zimelidine.svg
Clinical data
Trade names Zelmid
Routes of
administration 		Oral
ATC code
Legal status
Legal status
  • Withdrawn worldwide
Pharmacokinetic data
Elimination half-life 8.4±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  X mark.svgN 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C16H17BrN2
Molar mass 317.230 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- Yes check.svgY
  • Key:OYPPVKRFBIWMSX-SXGWCWSVSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Zimelidine (INN, BAN; brand names Zimeldine, Normud, Zelmid) , is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class, and the first SSRI antidepressant to be marketed. [2] It is a pyridylallylamine, and is structurally different from other antidepressants. [3]

Contents

Zimelidine was developed in the late 1970s and early 1980s by Arvid Carlsson, Hans Corrodi and Peter Berntsson, who were then working for the Swedish company Astra AB. Their work began with a series of antihistamines known as pheniramines that were found to block both serotonin and noradrenaline reuptake, and among these, brompheniramine was identified as the most potent serotonin reuptake blocker and was therefore selected as the starting point for their synthesis program, ultimately leading to the invention of zimelidine as a derivative of brompheniramine. [4] Zimelidine was first sold in 1982. [5]

While zimelidine had a very favorable safety profile comparing to other commonly used antidepressants like tricyclic antidepressants at the time it was developed, 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. [2] [5] [6] Its withdrawal, due to this unpredictable neurological side effect, marked a swift end to its clinical use despite its pioneering efficacy. [2] [4] After its withdrawal, it was succeeded by fluoxetine (derived from the antihistamine diphenhydramine) and fluvoxamine 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. [7] Zimelidine was able to improve cataplexy without causing daytime sleepiness. [7]

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. 1 2 3 "The Rise and Sudden Fall of Zimelidine: The First SSRI". CARLAT PUBLISHING. 2020-11-16. Retrieved 2026-01-16.
  3. ↑ 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.
  4. 1 2 Mulinari, Shai (2015). "Divergence and convergence of commercial and scientific priorities in drug development: The case of Zelmid, the first SSRI antidepressant". Social Science & Medicine. 138: 217–224. doi:10.1016/j.socscimed.2015.06.020 . Retrieved 2026-01-16.
  5. 1 2 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.
  6. ↑ 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.
  7. 1 2 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.