Antidepressant biochemical profile of the novel bicyclic compound Wy-45,030, an ethyl cyclohexanol derivative.
The novel bicyclic compound Wy-45,030 [1-2-(dimethylamino)-1-(4-methoxyphenyl)ethyl cyclohexanol, hydrochloride] exhibited a neurochemical profile predictive of antidepressant activity. Like the tricyclic antidepressants, it inhibited rat brain imipramine receptor binding and synaptosomal monoamine uptake (dopamine as well as norepinephrine and serotonin). It did not inhibit monoamine oxidase. Unlike the tricyclic antidepressants, it was not antimuscarinic in the guinea pig ileum, nor did it have any appreciable affinity for brain alpha-1 adrenergic or histamine-1 binding sites. Wy-45,030 was also without affinity for alpha-2 or beta adrenergic, benzodiazepine, serotonin-1, serotonin-2, dopamine-2, and opiate receptors. Such a profile is predictive of antidepressant activity devoid of the side-effects common to tricyclic therapy.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001681:Biological Assay; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003511:Cyclohexanols / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D006168:Guinea Pigs; D007099:Imipramine / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D000069470:Venlafaxine Hydrochloride
D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D008996:Monoamine Oxidase Inhibitors; D012701:Serotonin; D000069470:Venlafaxine Hydrochloride; D007099:Imipramine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine