Neurochemical properties of AHR-9377: a novel inhibitor of norepinephrine reuptake.
A novel potential antidepressant, AHR-9377, was evaluated for its inhibition of norepinephrine (NE), serotonin (5-HT) and dopamine (DA) reuptake in hypothalmic, cortical, and striatal rat synaptosomal preparations. AHR-9377 was found to be a potent, selective, noncompetitive inhibitor of NE reuptake. In addition, repeated injections of AHR-9377 caused a decrease in the density of beta adrenergic receptors in rat cerebral cortex. Little displacement by AHR-9377 at beta, alpha 1 and alpha 2 adrenergic, histaminergic, muscarinic, GABA-ergic, benzodiazepine of imipramine sites was observed. These pharmacological properties indicate that AHR-9377 may have clinical antidepressant activity with few side effects.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D003975:Diazepam / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium
D000928:Antidepressive Agents; D014316:Tritium; D001569:Benzodiazepines; C042692:tampramine fumarate; D007099:Imipramine; D003975:Diazepam; D009638:Norepinephrine