Zimelidine

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Zimelidine
Zimelidine.svg
Clinical data
Routes of
administration
Oral
ATC code
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  • Withdrawn worldwide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)
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C16H17BrN2
Molar mass 317.224 g/mol
3D model (JSmol)
 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.[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]

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. PMID 6228368. doi:10.2165/00003088-198308060-00004. 
  2. ^ Pubchem record
  3. ^ Barondes, Samuel H. Better Than Prozac. pp. 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 1028185Freely accessible. PMID 3156214. doi:10.1136/jnnp.48.1.65. 
  5. ^ Carlsson, A (2001). "A paradigm shift in brain research". Science. 294 (5544): 1021–4. Bibcode:2001Sci...294.1021C. PMID 11691978. doi:10.1126/science.1066969. 
  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. PMID 2950994. doi:10.1097/00002826-198602000-00004.