Zimelidine

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Zimelidine
Zimelidine.svg
Systematic (IUPAC) name
(Z)-3-(4-Bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine
Clinical data
Pregnancy cat.
  •  ?
Legal status
  • Withdrawn worldwide
Routes Oral
Pharmacokinetic data
Bioavailability ?
Metabolism ?
Half-life 8.4 +/- 2.0 hours (parent compound)
19.4 +/- 3.6 hours (norzimelidine)[1]
Excretion ?
Identifiers
CAS number 56775-88-3 N 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
ATC code N06AB02
PubChem [2] CID 5365247[2]
DrugBank DB04832
ChemSpider 4517305 YesY
UNII 3J928617DW YesY
ChEMBL CHEMBL37744 YesY
Chemical data
Formula C16H17BrN2 
Mol. mass 317.224
 N (what is this?)  (verify)

Zimelidine (Zimeldine, Normud, Zelmid) was the first selective serotonin reuptake inhibitor (SSRI) antidepressant to be marketed. It is a pyridylallylamine, and is structurally different from other antidepressants.[3]

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.[4]

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.[4][5] 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.[6] Zimelidine was able to improve cataplexy without causing daytime sleepiness.[6]

Side effects[edit]

Most often reported were:

Interactions[edit]

See also[edit]

References[edit]

  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. ^ Barondes, Samuel H. Better Than Prozac. p. 39–40. 
  4. ^ a b 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. PMC 1028185. 
  5. ^ 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. 
  6. ^ a b 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.