Zimelidine

Zimelidine
Systematic (IUPAC) name
(Z)-3-(4-Bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine
Clinical data
Routes of
administration		 Oral
Legal status
Legal status
  • Withdrawn worldwide
Pharmacokinetic data
Biological half-life 8.4±2 hours (parent compound)
19.4±3.6 hours (norzimelidine)[1]
Identifiers
CAS Number 56775-88-3 N 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
ATC code N06AB02 (WHO)
PubChem CID [2] 5365247[3]
DrugBank DB04832 YesY
ChemSpider 4517305 YesY
UNII 3J928617DW YesY
ChEMBL CHEMBL37744 YesY
Chemical data
Formula C16H17BrN2
Molar mass 317.224 g/mol
 NYesY (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.[4]

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.[5]

While zilmelidine 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.[5][6] 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.[7] Zimelidine was able to improve cataplexy without causing daytime sleepiness.[7]

Side effects

Most often reported were:

Interactions

See also

References

  1. ↑ Caille 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.
  2. ↑ Pubchem record
  3. ↑ Pubchem record
  4. ↑ Barondes, Samuel H. Better Than Prozac. pp. 39–40.
  5. 1 2 Fagius, J; Osterman, P. O.; Sidén, A; Wiholm, B. E. (1985). "Guillain-Barré syndrome following zimeldine treatment". Journal of Neurology, Neurosurgery, and Psychiatry 48 (1): 65–69. doi:10.1136/jnnp.48.1.65. PMC 1028185. PMID 3156214.
  6. ↑ Carlsson, A (2001). "A paradigm shift in brain research". Science 294 (5544): 1021–4. Bibcode:2001Sci...294.1021C. doi:10.1126/science.1066969. PMID 11691978.
  7. 1 2 Godbout R, Montplaisir J.; Montplaisir (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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