Alaproclate, a new selective 5-HT uptake inhibitor with therapeutic potential in depression and senile dementia.
Alaproclate, a new specific 5-HT uptake inhibitor, was examined for its action on several receptors in the brain, for its action on the NA, DA and 5-HT uptake mechanisms in vivo and for its action on brain biogenic amine content. Alaproclate was practically devoid of action on a number of receptors as examined in binding studies in vitro: 5-HT, histamine-H1, alpha 1, -alpha 2-adrenergic and dopamine D2 receptors. Alaproclate had also a weak affinity for 3H-norzimeldine binding sites in contrast to imipramine. Unlike the tricyclic antidepressants alaproclate had a negligible action on muscarinic receptors and failed to block muscarinic induced stimulation in vivo. Contrary to clomipramine alaproclate failed to block NA uptake in vivo. Alaproclate was found to display a regional selectivity in blocking 5-HT uptake in vivo (measured with the H 75/12-method). The compound was most potent in the hippocampus and hypothalamus followed by striatum and cerebral cortex with a low potency in the spinal cord. The results are discussed in relation to a previously presented carrier site model for serotonin reuptake.
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
D000929:Antidepressive Agents, Tricyclic; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C025293:alaproclate; D000409:Alanine; D004298:Dopamine; D009638:Norepinephrine