Zimelidine

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Zimelidine
Zimelidine.svg
Clinical data
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  • Withdrawn worldwide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
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)
InChI
 ☒NcheckY (what is this?)  

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 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.[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[]

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

Side effects[]

Most often reported were:

  • Dry mouth, dryness of pharyngeal and nasal membranes
  • Increased sweating (hyperhidrosis)
  • Vertigo
  • Nausea

Interactions[]

  • MAO inhibitors — severe or life-threatening reactions possible[medical citation needed]

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.
  2. ^ "Zimelidine". Pubchem. U.S. National Library of Medicine.
  3. ^ Barondes, Samuel H. Better Than Prozac. pp. 39–40.
  4. ^ Jump up to: 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.
  5. ^ 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.
  6. ^ Jump up to: 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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