title: Synthesis and antidepressant properties of novel 2-substituted 4,5-dihydro-1H-imidazole derivatives.
abstract: A unique combination of alpha 2-adrenoreceptor antagonist and serotonin-selective reuptake inhibitory activities has been identified in a series of 2-substituted 4,5-dihydro-1H-imidazole derivatives. This combination of blocking activities has provided one of these derivatives, napamezole hydrochloride (2), with potential as an antidepressant. A discussion of the syntheses of these compounds includes a convenient method for the conversion of nitriles to imidazolines with ethylenediamine and trimethylaluminum.
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D001763:Blepharoptosis / Q000139:chemically induced; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D019329:Idazoxan; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013747:Tetrabenazine / Q000037:antagonists & inhibitors; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors
chemical_list: D000928:Antidepressive Agents; D004146:Dioxanes; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin; D010133:p-Chloroamphetamine; D004298:Dopamine; D009638:Norepinephrine; D019329:Idazoxan; D013747:Tetrabenazine