Pharmacological and biochemical studies on a new compound, 2-(7-indeyloxymethyl)morpholine hydrochloride (YM-08054-1), and its derivatives with potential antidepressant properties.

Antidepressant properties of a new indene derivative, YM-08054-1, and its related compounds were compared with those of tricyclic antidepressants and viloxazine. The potencies of YM-08054-1 to inhibit uptake of both 14C-norepinephrine (14C-NE) and 14C-5-hydroxytryptamine (14C-5-HT) by the rat brain synaptosomes were similar to those of amitriptyline and imipramine. Other indene derivatives with an N-alkylated morpholine ring were proved to have less effect on the uptake of either 5-HT or NE than was YM-08054-1. YM-08054-1 was the most potent among all of the tested antidepressants in the inhibition of reserpine-induced facilitation of convulsions as well as in the potentiation of reserpine-induced facilitation of convulsions as well as in the potentiation of 5-hydroxytryptophan (5-HTP)-induced syndromes in mice, though the inhibitory effect of this agent on reserpine-induced hypothermia was weaker than that of either amitriptyline or desipramine, suggesting relatively selective effects of YM-08054-1 upon 5-HT rather than NE uptake in vivo. Neither viloxazine nor iprindole potentiated the responses to 5-HTP. YM-08054-1 was devoid of peripheral anticholinergic activity and exhibited weak local anesthetic effect as well as low acute toxicity when compared with amitriptyline. The results indicate that YM-08054-1 has a novel profile as an antidepressant agent which is quite different from that of either viloxazine or tricyclic compounds.