It is a pyridylallylamine, and is structurally different from other antidepressants.
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.
While zimelidine had a very favourable 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. 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.
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. Zimelidine was able to improve cataplexy without causing daytime sleepiness.
Most often reported were:
- Dry mouth, dryness of pharyngeal and nasal membranes.
- Increased sweating (hyperhidrosis).
MAO inhibitors – severe or life-threatening reactions possible.