Neuropharmacological Analysis of the Antidepressant Action of 2-[3-Methyl-7-(Thietan-3-Yl)-1-Ethylxanth-8-YLTHIO] Acetic Acid Hydrazide

Abstract

A compound with low toxicity and pronounced antidepressant activity upon single and long-term administration was discovered by us earlier among a series of new thietanylxanthine derivatives. The present article focused on the central mechanisms of action of 2-[3-methyl-7-(thietan-3-yl)-1-ethylxanth-7-ylthio]acetic acid hydrazide (laboratory code M-20). Neuropharmacological analysis showed that M-20 at doses of 0.97 and 12 mg/kg exhibited effects indicative of possible stimulatory action on adrenergic and inhibitory action on GABA-ergic neurotransmission in brains of outbred white mice. M-20 at a dose of 12 mg/kg produced an activating effect on the serotoninergic system in addition to action on the adrenergic and GABA-ergic systems and altered the activity of the cholinergic system. M-20 at doses of 0.97 and 12 mg/kg did not alter the effects of haloperidol and L-DOPA, which indicated that it did not influence dopaminergic neurotransmission and MAO-inhibiting activity. The results indicated that M-20 was promising (at the low dose) for use with depression associated with decreased activity of the serotoninergic system without side effects on the dopaminergic and cholinergic systems.