Iprindole
Iprindole, sold under the brand names Prondol, Galatur, and Tertran, is an atypical tricyclic antidepressant that has been used in the United Kingdom and Ireland for the treatment of depression but appears to no longer be marketed. It was developed by Wyeth and was marketed in 1967. The drug has been described by some as the first "second-generation" antidepressant to be introduced. However, it was very little-used compared to other TCAs, with the number of prescriptions dispensed only in the thousands.
Medical uses
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.On account of these interactions, caution should be used when combining iprindole with other drugs. As an example, when administered with amphetamine or methamphetamine, iprindole increases their brain concentrations and prolongs their terminal half-lives by 2- to 3-fold, strongly augmenting both their physiological effects and neurotoxicity in the process.
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. However, iprindole may not be as effective as other TCAs, particularly in terms of anxiolysis. 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. It is presumed to act as an inhibitor or antagonist/inverse agonist of all sites. Considering the range of its therapeutic concentrations, only the actions of iprindole on the 5-HT2 and histamine receptors might be anticipated to be of possible clinical significance. However, it is unknown whether these actions are in fact responsible for the antidepressant effects of iprindole. The plasma protein binding of iprindole and hence its free percentage and potentially bioactive concentrations do not seem to be known.