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We investigated the pharmacological characteristics of MO-8282 as a novel antidepressant. MO-8282 inhibited the specific binding of 3H-clonidine to cerebro-cortical membrane fractions from rats about five times more potently than mianserin, and it competed with clonidine in the twitch response of the isolated guinea-pig ileum under field stimulation. The results indicated that MO-8282 possessed alpha 2-adrenergic receptor blocking activity. MO-8282 in a dose of 30 mg/kg (p.o.) showed no inhibition against the uptake of noradrenaline, dopamine and serotonin in the rat brain, whereas mianserin inhibited the uptake of serotonin specifically. MO-8282, similar to mianserin, had no effect on spontaneous release of 3H-noradrenaline and slightly stimulated the release of 3H-serotonin from the rat cerebrocortical synaptosome. The turnover rate of noradrenaline in rat brain was accelerated by administration of MO-8282 (30 mg/kg) for 15 days; however, that of dopamine and serotonin was not affected. The above findings indicate that MO-8282, unlike tricyclic antidepressants, mainly exerts alpha 2-adrenoceptor blocking action on the central noradrenergic system, similar to mianserin. In addition, the fact that MO-8282 unlike mianserin showed no inhibition against uptake of serotonin in brain suggests that the alpha 2-adrenoceptor blocking of MO-8282 is more specific and potent than that of mianserin.
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