Has iprindole an alpha adrenergic activity?

1. Acute administration of iprindole potentiated the toxicity of 1-norepinephrine and increased the intensity of oxotremorine-induced tremors. 2. On the forced swimming test combination iprindole with imipramine reduced the duration of immobility. 3. The action of yohimbine on the locomotor activity was antagonized by a pre-injection of iprindole. 4. Iprindole increased and prolonged exophthalmia and loss of righting reflex induced by xylazine. 5 All these results seems indicate that iprindole has an indirect alpha 1 and alpha 2 adrenergic activity.

Is iprindole an indirect betamimetic drug?

Iprindole, an active antidepressant in clinical use, has no effect on norepinephrine reuptake and does not bind to receptors of the noradrenergic system. Iprindole weakly antagonizes reserpine hypothermia and potentiates yohimbine toxicity. This effect is antagonized by propranolol but not by atenolol or metoprolol. In an acute dose, iprindole potentiates the effect of maprotiline on yohimbine toxicity. Beta 2-adrenergic agonists and antagonists specifically modify the effect of iprindole on spontaneous motility. These results indicate that iprindole has an indirect beta 2-mimetic effect.

Effect of cysteine on the persistent depletion of brain monoamines by amphetamine, p-chloroamphetamine and MPTP.

The administration of L-cysteine (500 mg/kg i.p.) 30 min before and 5 h after the administration of (+)-amphetamine sulfate markedly attenuated the persistent decreases in striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rats one week after the administration of a single dose of amphetamine (9.2 mg/kg i.p.) to iprindole-treated animals and in mice one week after the last of four daily injections of amphetamine (30 mg/kg i.p.). Cysteine prevented the persistent decreases in striatal serotonin (5HT) and 5-hydroxyindoleacetic acid (5HIAA) one week after the administration of p-chloroamphetamine to rats, but failed to alter the persistent decreases in striatal DA, DOPAC and HVA in mice one week after the last of four daily doses of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 30 mg/kg s.c.). The results suggest that the mechanisms by which amphetamine and p-chloroamphetamine, but not MPTP, produce persistent depletions of striatal monoamines involve the generation of neurotoxic electrophilic intermediates which can be inactivated by the administration of cysteine.

Chronic treatment with iprindole reduces immobility of rats in the behavioural 'despair' test by activating dopaminergic mechanisms in the brain.

Iprindole, 10 mg kg-1 i.p., once daily for 21 days, enhanced the metabolism of dopamine in the frontal cortex and striatum of rats with no effect in the nucleus accumbens 1 h after the last injection. Noradrenaline metabolism in the brainstem and telencephalon was also increased in these conditions. No effect on dopamine or noradrenaline metabolism was seen 24 h after the last injection. The same repeated treatment schedule with iprindole markedly reduced the immobility of rats in the behavioural 'despair' test 1 h after the last injection and the effect was prevented by 0.5 mg kg-1 i.p. haloperidol and 100 mg kg-1 i.p. sulpiride but not by 3 mg kg-1 s.c. prazosin or 5 mg kg-1 i.p. (+/-)-propranolol. The data show that enhanced metabolism of brain dopamine and noradrenaline is associated with the presence of iprindole during repeated treatment and the effect on dopamine mechanism is important in iprindole's ability to reduce rats' immobility in the behavioural 'despair' test.