Assessment |
Biopsychology |
Comparative |
Cognitive |
Developmental |
Language |
Individual differences |
Personality |
Philosophy |
Social |
Methods |
Statistics |
Clinical |
Educational |
Industrial |
Professional items |
World psychology |
Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
Zimelidine chemical structure | |
3-(4-bromophenyl)-N,N-dimethyl-3-pyridin-3-yl-prop-2-en-1-amine IUPAC name | |
CAS number 56775-88-3 |
ATC code |
PubChem 41987 |
DrugBank [1] |
Chemical formula | {{{chemical_formula}}} |
Molecular weight | 317.224 |
Bioavailability | ? |
Metabolism | ? |
Elimination half-life | 8.4 +/- 2.0 hours (parent compound) 19.4 +/- 3.6 hours (norzimelidine) |
Excretion | ? |
Pregnancy category | ? |
Legal status | Withdrawn from market |
Routes of administration | Oral |
Zimelidine (Normud®, Zelmid®) was the first marketed selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a pyridylallylamine, structurally different from other antidepressants. The substance was developed in the early 1980s by the Swedish company AstraZeneca following a search for drugs with structures similar to chlorpheniramine (it is a derivative of brompheniramine), an antihistamine with antidepressant activity. It was then licensed to other drug producers.
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.[2] Zimelidine was able to improve cataplexy without causing daytime sleepiness.[3]
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[]
- 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.
- ^ 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
Further references[]
- Alhaider, A. A., & Mustafa, A. A. (1991). Enhancement of imipramine-induced rat brain !b-adrenoreceptor desensitization by subacute co-administration of trazodone, zimelidine, quipazine or 5-hydroxytryptophan: Psychopharmacology Vol 103(3) Mar 1991, 351-356.
- Ansseau, M., Papart, P., Pitchot, W., Timsit-Berthier, M., & et al. (1992). Dexamethasone suppression test and prediction of treatment response to selective antidepressants: European Psychiatry Vol 7(4) 1992, 191-194.
- Audi, E. A., de Aguiar, J. C., & Graeff, F. G. (1988). Mediation by serotonin of the antiaversive effect of zimelidine and propranolol injected into the dorsal midbrain central grey: Journal of Psychopharmacology Vol 2(1) 1988, 26-32.
- Balldin, J., Berggren, U., Bokstrom, K., Eriksson, M., & et al. (1994). Six-month open trial with Zimelidine in alcohol-dependent patients: Reduction in days of alcohol intake: Drug and Alcohol Dependence Vol 35(3) Jun 1994, 245-248.
- Barber, N. I., Teicher, M. H., & Baldessarini, R. J. (1989). Effects of selective monoaminergic reuptake blockade on activity rhythms in developing rats: Psychopharmacology Vol 97(3) Mar 1989, 343-348.
- Bayley, P. J., Bentley, G. D., & Dawson, G. R. (1998). The effects of selected antidepressant drugs on timing behavior in rats: Psychopharmacology Vol 136(2) Mar 1998, 114-122.
- Bengtsson, B.-O., Lundmark, J., & Walinder, J. (1991). No crossover reactions to citalopram or paroxetine among patients hypersensitive to zimeldine: British Journal of Psychiatry Vol 158 Jun 1991, 853-855.
- Bjorvatn, B., Neckelmann, D., & Ursin, R. (1992). The 5-HT-sub(1A) antagonist (Lambda )-alprenolol fails to modify sleep or zimeldine-induced sleep-waking effects in rats: Pharmacology, Biochemistry and Behavior Vol 42(1) May 1992, 49-56.
- Fasmer, O. B., Post, C., & Hole, K. (1987). Changes in nociception after acute and chronic administration of zimelidine: Different effects in the formalin test and the substance P behavioural assay: Neuropharmacology Vol 26(4) Apr 1987, 309-312.
- Gill, K., & Amit, Z. (1987). Effects of serotonin uptake blockade on food, water, and ethanol consumption in rats: Alcoholism: Clinical and Experimental Research Vol 11(5) Oct 1987, 444-449.
- Gunturkun, O., Grothues, A., Hautkappe, A., Vise, F., & et al. (1989). Serotonergic modulation of ingestive behavior in pigeons: Pharmacology, Biochemistry and Behavior Vol 32(2) Feb 1989, 415-420.
- Hilakivi, L. A., & Hilakivi, I. (1987). Increased adult behavioral "despair" in rats neonatally exposed to desipramine or zimeldine: An animal model of depression? : Pharmacology, Biochemistry and Behavior Vol 28(3) Nov 1987, 367-369.
- Kleinlogel, H., & Burki, H. R. (1987). Effects of the selective 5-hydroxytryptamine uptake inhibitors paroxetine and zimeldine on EEG sleep and waking stages in the rat: Neuropsychobiology Vol 17(4) 1987, 206-212.
- Kristofferson, A., Sohl-Akerlund, A., Hall, E., Bengtsson, B. O., & et al. (1994). Effect of zimeldine and its metabolites on: International Clinical Psychopharmacology Vol 9(3) Sep 1994, 179-185.
- Lesko, L. J., Fiore, D., Leslie, J., Narang, P. K., & et al. (1986). Estimation of protein binding of zimelidine and norzimelidine using cerebrospinal fluid and ultrafiltration: Research Communications in Psychology, Psychiatry & Behavior Vol 11(2-3) 1986, 95-111.
- Linnoila, M., Guthrie, S., Lane, E. A., Karoum, F., & et al. (1986). Clinical studies on norepinephrine metabolism: How to interpret the numbers: Psychiatry Research Vol 17(3) Mar 1986, 229-239.
- Lund, A., Mjellem-Joly, N., & Hole, K. (1991). Chronic administration of desipramine and zimelidine changes the behavioural response in the formalin test in rats: Neuropharmacology Vol 30(5) May 1991, 481-487.
- Lund, A., Tjolsen, A., & Hole, K. (1990). Antinociceptive effect of intrathecally-administered desipramine and zimelidine in rats: Neuropharmacology Vol 29(9) Sep 1990, 819-823.
- Maudhuit, C., Hamon, M., & Adrien, J. (1996). Effects of chronic treatment with zimelidine and REM sleep deprivation on the regulation of raphe neuronal activity in a rat model of depression: Psychopharmacology Vol 124(3) Apr 1996, 267-274.
- Maudhuit, C., Prevot, E., Dangoumau, L., Martin, P., Hamon, M., & Adrien, J. (1997). Antidepressant treatment in helpless rats: Effect on the electrophysiological activity of raphe dorsalis serotonergic neurons: Psychopharmacology Vol 130(3) Apr 1997, 269-275.
- McMahon, T. F., Weiner, M., Lesko, L., & Emm, T. (1987). Effects of age on antidepressant kinetics and memory in Fischer 344 rats: Pharmacology, Biochemistry and Behavior Vol 26(2) Feb 1987, 313-319.
- Melo, L. L., & Brandao, M. L. (1995). Involvement of 5-HT-sub(1A ) and 5-HT-sub-2 receptors of the inferior colliculus in aversive states induced by exposure of rats to the elevated plus-maze test: Behavioural Pharmacology Vol 6(4) Jun 1995, 413-417.
- Montgomery, S. A., Gabriel, R., James, D., Hawley, C., & et al. (1989). Hypersensitivity to zimelidine without cross reactivity to fluoxetine: International Clinical Psychopharmacology Vol 4(Suppl 1) Jan 1989, 27-29.
- Montgomery, S. A., Gabriel, R., James, D., Hawley, C., & et al. (1989). The specificity of the zimelidine reaction: International Clinical Psychopharmacology Vol 4(1) Jan 1989, 19-23.
- Nystrom, C., & Hallstrom, T. (1987). Comparison between a serotonin and a noradrenaline reuptake blocker in the treatment of depressed outpatients: A cross-over study: Acta Psychiatrica Scandinavica Vol 75(4) Apr 1987, 377-382.
- Perrault, G., Morel, E., Zivkovic, B., & Sanger, D. J. (1992). Activity of litoxetine and other serotonin uptake inhibitors in the tail suspension test in mice: Pharmacology, Biochemistry and Behavior Vol 42(1) May 1992, 45-47.
- Sletvold, H., & Gotestam, K. G. (1989). Placebo and antidepressive effects: Zimelidine and doxepin in a double-blind extended placebo study on outpatients with minor depression: European Journal of Psychiatry Vol 3(3) Jul-Sep 1989, 151-156.
- Sommerfelt, L., & Ursin, R. (1987). The effects of zimeldine and alaproclate combined with a small dose of 5-HTP on waking and sleep stages in cats: Behavioural Brain Research Vol 24(1) Apr 1987, 1-10.
- Sommerfelt, L., & Ursin, R. (1993). The 5-HT-sub-2 antagonist ritanserin decreases sleep in cats: Sleep: Journal of Sleep Research & Sleep Medicine Vol 16(1) Jan 1993, 15-22.
- von Knorring, L., & Mornstad, H. (1986). Saliva secretion rate and saliva composition as a model to determine the effect of antidepressant drugs on cholinergic and noradrenergic transmission: Neuropsychobiology Vol 15(3-4) Sep 1986, 146-154.
- Zagrodzka, J., Wieczorek, M., & Romaniuk, A. (1994). Social interactions in rats: Behavioral and neurochemical alterations in DSP-4-treated rats: Pharmacology, Biochemistry and Behavior Vol 49(3) Nov 1994, 541-548.
External links[]
- PubChem Substance Summary: Zimelidine National Center for Biotechnology Information.
fr:zimelidine
This page uses Creative Commons Licensed content from Wikipedia (view authors). |