Iprindole

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Iprindole
Iprindole-structure.png
Iprindole3Dan.gif
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 cat.
  •  ?
Legal status
  • Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic[1]
Half-life 52.5 hours[2]
Excretion Urine, Feces[3]
Identifiers
CAS number 5560-72-5 YesY
ATC code N06AA13
PubChem CID 21722
ChemSpider 20417 YesY
UNII 69U0IKR8FP YesY
KEGG D04605 YesY
ChEMBL CHEMBL126224 YesY
Chemical data
Formula C19H28N2 
Mol. mass 284.439 g/mol
 YesY (what is this?)  (verify)

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 an antagonist of 5-HT2 receptors, 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[edit]

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

It has been discontinued throughout the world.

Chemistry[edit]

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[edit]

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[edit]

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

Side effects[edit]

Anticholinergic side effects such as dry mouth and constipation are either greatly reduced in comparison to imipramine and most other TCAs 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[edit]

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

Interactions[edit]

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 physiological effects and neurotoxicity in the process.[45][46][47]

Overdose[edit]

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 deaths associated with iprindole were recorded in the United Kingdom, whereas 278 were reported for imipramine.[48] However, it should be noted that imipramine is prescribed much more often than iprindole, and for that reason this comparison is likely not entirely representative of iprindole's true capacity for fatality in overdose.

See also[edit]

References[edit]

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Further reading[edit]