Zimelidine
Clinical data | |
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Routes of administration |
Oral |
ATC code | N06AB02 (WHO) |
Legal status | |
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Pharmacokinetic data | |
Biological half-life | 8.4±2 hours (parent compound) 19.4±3.6 hours (norzimelidine)[1] |
Identifiers | |
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CAS Number | 56775-88-3 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate) |
PubChem (CID) | [2] 5365247[2] |
DrugBank | DB04832 |
ChemSpider | 4517305 |
UNII | 3J928617DW |
ChEMBL | CHEMBL37744 |
Chemical and physical data | |
Formula | C16H17BrN2 |
Molar mass | 317.224 g/mol |
3D model (Jmol) | Interactive image |
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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 zilmelidine 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[edit]
The mode of action is a strong reuptake inhibition of serotonin from the synaptic cleft. Postsynaptic receptors are not acted upon.
Other uses[edit]
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[edit]
Most often reported were:
- Dry mouth, dryness of pharyngeal and nasal membranes
- Increased sweating (hyperhidrosis)
- Vertigo
- Nausea
Interactions[edit]
- MAO inhibitors — severe or life-threatening reactions possible[medical citation needed]
References[edit]
- ^ 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.
- ^ Pubchem record
- ^ Barondes, Samuel H. Better Than Prozac. pp. 39–40.
- ^ a b Fagius, J; Osterman, P. O.; Sidén, A; Wiholm, B. E. (1985). "Guillain–Barré syndrome following zimeldine treatment". Journal of Neurology, Neurosurgery, and Psychiatry. 48 (1): 65–69. doi:10.1136/jnnp.48.1.65. PMC 1028185. PMID 3156214.
- ^ Carlsson, A (2001). "A paradigm shift in brain research". Science. 294 (5544): 1021–4. Bibcode:2001Sci...294.1021C. doi:10.1126/science.1066969. PMID 11691978.
- ^ a b Godbout R, Montplaisir J.; Montplaisir (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.