Zimelidine

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.^[2]

Zimelidine

Clinical data
Trade names	Zelmid
Routes of administration	Oral
ATC code	N06AB02 (WHO)
Legal status
Legal status	Withdrawn worldwide
Pharmacokinetic data
Elimination half-life	8.4±2 hours (parent compound) 19.4±3.6 hours (norzimelidine)[1]
Identifiers
IUPAC name (Z)-3-(4-Bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine
CAS Number	56775-88-3 N 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)
PubChem CID	5365247
DrugBank	DB04832 Y
ChemSpider	4517305 Y
UNII	3J928617DW
ChEMBL	ChEMBL37744 Y
CompTox Dashboard (EPA)	DTXSID6048462
Chemical and physical data
Formula	C16H17BrN2
Molar mass	317.230 g·mol−1
3D model (JSmol)	Interactive image
SMILES Brc2ccc(C(=C/CN(C)C)/c1cccnc1)cc2
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
NY (what is this?)  (verify)

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 invented 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.^[3]

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.^[3][4] 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.^[5] Zimelidine was able to improve cataplexy without causing daytime sleepiness.^[5]

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

• Ranitidine
• RTI-353
• Triprolidine
• SB-649,915