Zimelidine

Zimelidine

Systematic (IUPAC) name
3-(4-bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine
Clinical data
Pregnancy cat.	?
Legal status	Rx Only, Withdrawn worldwide
Routes	Oral
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half-life	8.4 +/- 2.0 hours (parent compound) 19.4 +/- 3.6 hours (norzimelidine)
Excretion	?
Identifiers
CAS number	56775-88-3 Y 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
ATC code	N06AB02
PubChem	CID 5365247
DrugBank	DB04832
ChemSpider	4517305 Y
UNII	3J928617DW N
ChEMBL	CHEMBL37744 Y
Chemical data
Formula	C16H17BrN2
Mol. mass	317.224
SMILES	eMolecules & PubChem
InChI 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- Y Key:OYPPVKRFBIWMSX-SXGWCWSVSA-N Y
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.

Zimelidine was developed in the 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.

Zimelidine has been banned worldwide due to serious, sometimes fatal, cases of central and/or peripheral neuropathy known as Guillain-Barré syndrome and due to a peculiar hypersensitivity reaction involving many organs including skin exanthema, flu-like symptoms, arthralgias, and sometimes eosinophilia. Additionally, zimelidine was charged to cause an increase in suicidal ideation and/or attempts among depressive patients. After its ban, 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.^[1] Zimelidine was able to improve cataplexy without causing daytime sleepiness.^[2]

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

Dosage

The former doses were 200 to 400 mg daily in outpatients and up to 600mg in inpatients.

See also

• Alaproclate
• Indalpine

References

• PubChem Substance Summary: Zimelidine National Center for Biotechnology Information.

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. ^ 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. 
3. ^ see Godbout et al. 1986