zimelidine

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 470635867

| IUPAC_name = (Z)-3-(4-Bromophenyl)-N,N-dimethyl-3-(pyridin-3-yl)prop-2-en-1-amine

| image = Zimelidine.svg

| image_class = skin-invert-image

| width = 222

| tradename = Zelmid

| pregnancy_category =

| legal_status = Withdrawn worldwide

| routes_of_administration = Oral

| bioavailability =

| metabolism =

| elimination_half-life = 8.4±2 hours (parent compound)
19.4±3.6 hours (norzimelidine){{cite journal | vauthors = Caillé G, Kouassi E, de Montigny C | title = Pharmacokinetic study of zimelidine using a new GLC method | journal = Clinical Pharmacokinetics | volume = 8 | issue = 6 | pages = 530–40 | year = 1986 | pmid = 6228368 | doi = 10.2165/00003088-198308060-00004 | s2cid = 42052631 }}

| excretion =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 56775-88-3

| CAS_supplemental = 60525-15-7 (anhydrous dihydrochloride), 61129-30-4 (dihydrochloride monohydrate)

| ATC_prefix = N06

| ATC_suffix = AB02

| PubChem = 5365247

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB04832

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4517305

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 3J928617DW

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 37744

| C=16 | H=17 | Br=1 | N=2

| smiles = Brc2ccc(C(=C/CN(C)C)/c1cccnc1)cc2

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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-

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = OYPPVKRFBIWMSX-SXGWCWSVSA-N

}}

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.{{Cite book |last=Barondes |first=Samuel H. |title=Better than Prozac: Creating the Next Generation of Psychiatric Drugs |date=2005-01-26 |publisher=Oxford University Press |isbn=978-0-19-517979-8 |pages=39–40 |language=English}}

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.{{cite journal | vauthors = Fagius J, Osterman PO, Sidén A, Wiholm BE | title = Guillain-Barré syndrome following zimeldine treatment | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 48 | issue = 1 | pages = 65–9 | date = January 1985 | pmid = 3156214 | pmc = 1028185 | doi = 10.1136/jnnp.48.1.65 }}

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.{{cite journal | vauthors = Carlsson A | title = A paradigm shift in brain research | journal = Science | volume = 294 | issue = 5544 | pages = 1021–4 | date = November 2001 | pmid = 11691978 | doi = 10.1126/science.1066969 | bibcode = 2001Sci...294.1021C | s2cid = 24365669 }} 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.{{cite journal | vauthors = Godbout R, Montplaisir J | title = The effect of zimelidine, a serotonin-reuptake blocker, on cataplexy and daytime sleepiness of narcoleptic patients | journal = Clinical Neuropharmacology | volume = 9 | issue = 1 | pages = 46–51 | year = 1986 | pmid = 2950994 | doi = 10.1097/00002826-198602000-00004 }} Zimelidine was able to improve cataplexy without causing daytime sleepiness.