Zimelidine
| File:Zimelidine.png | |
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| Routes of administration | Oral |
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| Bioavailability | ? |
| Metabolism | ? |
| Elimination half-life | 8.4 +/- 2.0 hours (parent compound) 19.4 +/- 3.6 hours (norzimelidine) |
| Excretion | ? |
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| Formula | C16H17BrN2 |
| Molar mass | 317.224 g·mol−1 |
Zimelidine (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 400mg daily in outpatients and up to 600mg in inpatients.
References
- PubChem Substance Summary: Zimelidine National Center for Biotechnology Information.
- Bruce G. Charlton, Self-management of psychiatric symptoms using over-the-counter (OTC) psychopharmacology: the S-DTM therapeutic model - self-diagnosis, self-treatment, self-monitoring. Medical Hypotheses 2005; 65: 823-828.
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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. PMID 2950994.
- ^ see Godbout et al. 1986