Iprindole: Wikis


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Iprindole
Systematic (IUPAC) name
3-(6,7,8,9,10,11-hexahydro-5H-cycloocta[b]indol-5-yl)-N,N-dimethylpropan-1-amine
Identifiers
CAS number 5560-72-5
ATC code N06AA13
PubChem 21722
Chemical data
Formula C19H28N2 
Mol. mass 284.439 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Half life 52.5 hours[1]
Excretion Urine, Feces[2]
Therapeutic considerations
Pregnancy cat. None
Legal status Prescription only
Routes Oral

Iprindole (Prondol, Galatur, Tertran), formerly known as pramindole, is a tricyclic antidepressant (TCA) used in Europe but not the United States for the treatment of depression.[3][4][5] It was introduced by Wyeth and has been used clinically since 1967.[6] Notably, iprindole was the first second-generation antidepressant to be launched.[7]

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'.[8][9][10] Additionally, side effects of iprindole are much less prominent relative to other TCAs and it is well-tolerated.[11] However, iprindole's efficacy may not be as great as other TCAs, especially in regards to anxiety relief.[8][12]

Contents

Availability

Iprindole is sold under the trade name Prondol by Wyeth in the United Kingdom and Ireland for the indication of major depressive disorder.[13] It has also been sold as Galatur and Tertran by Wyeth as well.[14] 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.[11][15]

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.[31][32][33][34]

Dosage

Iprindole is used in doses of 30-180 mg daily.[3][35]

Side effects

Anticholinergic side effects such as dry mouth and constipation are either greatly reduced in comparison to imipramine or fully lacking with iprindole.[11] 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.[12]

Iprindole has been associated with jaundice and hepatotoxicity and should not be taken by alcoholics or people with pre-existing liver disease.[36][37][38][6] 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.[39][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.[39] 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 their dopaminergic and serotonergic 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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  2. ^ Sisenwine SF, Tio CO, Ruelius HW (April 1979). "The disposition of [14Ciprindole in man, dog, miniature swine, rhesus monkey and rat"]. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 9 (4): 237–46. doi:10.3109/00498257909038726. PMID 113942. http://informahealthcare.com/doi/abs/10.3109/00498257909038726. 
  3. ^ a b Ayd, Frank J. (2000). Lexicon of psychiatry, neurology, and the neurosciences. Philadelphia, Pa: Lippincott-Williams & Wilkins. ISBN 0-7817-2468-6. http://books.google.com/books?id=ea_QVG2BFy8C&lpg=PA531&dq=iprindole&as_brr=3&pg=PA531#v=onepage&q=iprindole&f=false. 
  4. ^ Dictionary of organic compounds. London: Chapman & Hall. 1996. ISBN 0-412-54090-8. http://books.google.com/books?id=x2Su3GKCvtsC&lpg=PA3975&dq=iprindole%20prondol&as_brr=3&pg=PA3975#v=onepage&q=&f=false. 
  5. ^ Davison, Gerald C.; Hooley, Jill M.; Neale, John M. (1989). Readings in abnormal psychology. New York: Wiley. ISBN 0-471-63107-8. http://books.google.com/books?id=jYhnhQ4X-e8C&lpg=PA186&dq=iprindole%20trimipramine&lr=&as_brr=3&pg=PA186#v=onepage&q=iprindole&f=false. 
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