Iprindole

Iprindole was used in the treatment of major depressive disorder in dosages similar to those of other TCAs. ==Contraindications==

Iprindole has been associated with jaundice and hepatotoxicity and should not be taken by alcoholics or people with pre-existing liver disease. If such symptoms are encountered iprindole should be discontinued immediately. ==Side effects==

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. However, it still has significant antihistamine effects and therefore can produce sedation, though this is diminished relative to other TCAs similarly. Iprindole also lacks significant alpha-blocking properties, and hence does not pose a risk of orthostatic hypotension. ==Overdose==

In overdose, iprindole is much less toxic than most other TCAs and is considered relatively benign. For instance, between 1974 and 1985, only two deaths associated with iprindole were recorded in the United Kingdom, whereas 278 were reported for imipramine, although imipramine is used far more often than iprindole. == 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. It also inhibits its own metabolism. ==Pharmacology==

Pharmacodynamics Iprindole is unique compared to most other TCAs in that it is a very weak and negligible inhibitor of the reuptake of serotonin and norepinephrine and appears to act instead as a selective albeit weak antagonist of 5-HT2 receptors; hence its classification by some as "second-generation". Additionally, iprindole has very weak/negligible antiadrenergic and anticholinergic activity and weak although possibly significant antihistamine activity; as such, side effects of iprindole are much less prominent relative to other TCAs, and it is well tolerated. Based on animal research, the antidepressant effects of iprindole may be mediated through downstream dopaminergic mechanisms. The binding affinities of iprindole for various biological targets are presented in the table to the right. A single oral dose of 60 mg iprindole to healthy volunteers has been found to achieve mean peak plasma concentrations of 67.1 ng/mL (236 nmol/L) after 2 to 4 hours. The mean terminal half-life of iprindole was 52.5 hours, which is notably much longer than that of other TCAs like amitriptyline and imipramine. Following chronic treatment with 90 mg/day iprindole for 3 weeks, plasma concentrations of the drug ranged between 18 and 77 ng/mL (63–271 nmol/L). Theoretical steady-state concentrations should be reached by 99% within 15 to 20 days of treatment. ==Chemistry==

Iprindole is a tricyclic compound, specifically a cyclooctaindole (that is, an indole nucleus joined with a cyclooctyl ring), and possesses three rings fused together with a side chain attached in its chemical structure. It is a tertiary amine TCA, although its ring system and pharmacological properties are very different from those of other TCAs. Other tertiary amine TCAs that are similar to iprindole include butriptyline and trimipramine. The chemical name of iprindole is 3-(6,7,8,9,10,11-hexahydro-5H-cycloocta[b]indol-5-yl)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H28N2 with a molecular weight of 284.439 g/mol. The drug has been used commercially as both the free base and the hydrochloride salt. The CAS Registry Number of the free base is 5560-72-5 and of the hydrochloride is 20432–64–8. ==History==

Iprindole was developed by Wyeth and was marketed in 1967. ==Society and culture==

Generic names Iprindole is the English and French generic name of the drug and its , , , and , while iprindole hydrochloride is its . Its generic name in Spanish and German is iprindol while its generic name in Latin is iprindolum. and has also been sold as Galatur and Tertran by Wyeth. Availability Iprindole was previously available in the United Kingdom and Ireland but seems to no longer be available for medical use in any country. == References ==