Iprindole

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Iprindole
160px
Systematic (IUPAC) name
3-(6,7,8,9,10,11-hexahydro- 5H-cycloocta[b]indol-5-yl)- N,N-dimethylpropan- 1-amine
Clinical data
Pregnancy
category
  •  ?
Routes of
administration
Oral
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic[1]
Biological half-life 52.5 hours[2]
Excretion Urine, Feces[3]
Identifiers
CAS Number 5560-72-5
ATC code N06AA13 (WHO)
PubChem CID 21722
ChemSpider 20417
Chemical data
Formula C19H28N2
Molar mass 284.439 g/mol[[Script error: No such module "String".]]
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Iprindole (Prondol, Galatur, Tertran), formerly known as pramindole, is a tricyclic antidepressant (TCA) used in Europe for the treatment of depression.[4][5][6] It was introduced by Wyeth and has been used clinically since 1967.[7] Notably, iprindole was the first second-generation antidepressant to be launched.[8]

Iprindole is unique compared to most other TCAs in that it is a relatively weak inhibitor of the reuptake of serotonin and norepinephrine and instead acts predominantly as a 5-HT2 receptor antagonist, hence its classification as 'second-generation'.[9][10][11] Additionally, side effects of iprindole are much less prominent relative to other TCAs and it is well-tolerated.[12] However, iprindole's efficacy may not be as great as other TCAs, especially in regards to anxiety relief.[9][13]

Availability

Iprindole is sold under the trade name Prondol by Wyeth in the United Kingdom and Ireland for the indication of major depressive disorder.[14] It has also been sold as Galatur and Tertran by Wyeth as well.[15] It is unclear whether iprindole is available in any other countries.

Chemistry

On a structural level, iprindole differs from other TCAs in that it contains an indole nucleus, similarly to the heterocyclic antipsychotic oxypertine, and has an eight-membered and saturated third ring.[12][16]

Pharmacology

Iprindole acts as an antagonist (or inverse agonist) at the following receptors:

And as an inhibitor of the following transporters:

It has negligible affinity (>10,000 nM) for β-adrenergic and sigma receptors.[32][33][34][35]

Dosage

Iprindole is used in doses of 30-180 mg daily.[4][36]

Side effects

Anticholinergic side effects such as dry mouth and constipation are either greatly reduced in comparison to imipramine or fully lacking with iprindole.[12] However, it still has potent antihistamine effects and therefore can produce sedation, though this is diminished relative to imipramine as well, perhaps due to iprindole lacking significant alpha-blocking properties.[13]

Contraindications

Iprindole has been associated with jaundice and hepatotoxicity and should not be taken by alcoholics or people with pre-existing liver disease.[37][38][39][7] If such symptoms are encountered iprindole should be discontinued immediately.

Interactions

Iprindole has been shown to be a potent inhibitor of the aromatic hydroxylation and/or N-dealkylation-mediated metabolism of many substances including, but not limited to octopamine, amphetamine, methamphetamine, fenfluramine, phenelzine, tranylcypromine, trimipramine, and fluoxetine, likely via inactivating cytochrome P450 enzymes.[1][40][41][42][43][44] It also inhibits its own degradation.[43]

On account of these interactions, caution should be used when combining iprindole with other drugs.[1] As an example, when administered with amphetamine or methamphetamine, iprindole increases their brain concentrations and prolongs their half-lives by 2- to 3-fold, strongly augmenting both their effects and neurotoxicity in the process.[45][46][47]

Overdose

In overdose, iprindole is much less toxic than most other TCAs and is considered relatively benign.[48] For instance, between 1974 and 1985, only two fatalities associated with iprindole were recorded in the United Kingdom, whereas 278 were reported for imipramine.[48]

See also

References

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Further reading

  • de Montigny C (1982). "Iprindole: a cornerstone in the neurobiological investigation of antidepressant treatments". Modern Problems of Pharmacopsychiatry. 18: 102–16. PMID 6285182. 
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  1. 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  2. Caillé G, de Montigny C, Besner JG (1982). "Quantitation of iprindole in plasma by GLC". Biopharmaceutics & Drug Disposition. 3 (1): 11–7. doi:10.1002/bdd.2510030103. PMID 7082775. 
  3. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  4. 4.0 4.1 Ayd, Frank J. (2000). Lexicon of psychiatry, neurology, and the neurosciences. Philadelphia, Pa: Lippincott-Williams & Wilkins. ISBN 0-7817-2468-6. 
  5. Dictionary of organic compounds. London: Chapman & Hall. 1996. ISBN 0-412-54090-8. 
  6. Davison, Gerald C.; Hooley, Jill M.; Neale, John M. (1989). Readings in abnormal psychology. New York: Wiley. ISBN 0-471-63107-8. 
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  12. 12.0 12.1 12.2 "Progress in medicinal chemistry - Google Books". 
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  14. Sean C. Sweetman (2009). Martindale: The Complete Drug Reference, 36th Edition. London: Pharmaceutical Press. ISBN 0-85369-840-6. 
  15. "DrugFuture.com - Iprindole". 
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  33. Ganry H, Bourin M (1988). "Is iprindole an indirect betamimetic drug?". Neuropsychobiology. 20 (4): 187–93. doi:10.1159/000118497. PMID 2908249. 
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  36. Wing, Lorna; Wing, J. K. (1982). Psychoses of uncertain aetiology. Cambridge, UK: Cambridge University Press. ISBN 0-521-28438-4. 
  37. Aronson, Jeffrey Kenneth (2008). Meyler's Side Effects of Psychiatric Drugs (Meylers Side Effects). Amsterdam: Elsevier Science. ISBN 0-444-53266-8. 
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  44. Aspeslet LJ, Baker GB, Coutts RT, Torok-Both GA (1994). "The effects of desipramine and iprindole on levels of enantiomers of fluoxetine in rat brain and urine". Chirality. 6 (2): 86–90. doi:10.1002/chir.530060208. PMID 8204417. 
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