Susan T. Nielsen

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.

A potent gastric acid anti-secretory histamine H2 receptor antagonist, N-[2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]-ethyl]thieno[3,4-d]isothiazol-3-amine 1,1-dioxide, hydrochloride (Wy-45,727)

Abstract The synthesis of the title compound, a new histamine H2-receptor antagonist (pA2 = 8.2), (Wy-45,727; 7) is described. Its gastric acid anti-secretory potencies in the rat and dog were found to be significantly greater than those of cimetidine or ranitidine.