The effect of new derivatives of tietan-1,1-dioxide on some mediator systems of the brain

Aim. To study the effect of new derivatives of 3 substituted tietan-1,1-dioxide on some mediator systems of the brain in order to determine the possible mechanism of antidepressant effect of these compounds. Methods. In an experiment with male mice studied was the effect of three most active derivatives of tietan-1,1-dioxide, which exhibit antidepressant properties [3 methooxytietan-1,1-dioxide (H14), 3-(2-isopropoxy-5-methylphenoxy)-tietan-1,1-dioxide (H40) and 3-phenylsulphonyltietan-1,1-dioxide (N69)] on the neurotransmitter systems of the brain. In the experiments used were the tests of pharmacological interaction with a sympatholytic reserpine, with a nonselective agonist of dopamine receptors apomorphine, with a dopamine receptor antagonist haloperidol, with a precursor of serotonin 5-oxytryptophan, with a precursor of dopamine levodopa, with an α2-adrenoceptor agonist clonidine, and with an agonist of M-cholinoceptors arecoline. Results. It has been shown that the spectrum of neuropharmacological effects of new derivatives of tietan-1,1-dioxide (H14, H40, N69) is diverse and is associated with the effects on the adrenergic, dopaminergic and serotonergic brain structures. Thus, H14 reduces the severity of hypothermia induced by reserpine, apomorphine, clonidine, and levodopa, as well as the severity of reserpine ptosis, haloperidol catalepsy and 5- oxytryptophan hyperkinesis. H40, in contrast to H14, has no effect on haloperidol catalepsy and hypothermia induced by levodopa, while H69 has no effect on clonidine-induced hypothermia. All the compounds do not alter the latent period and duration of the arecoline tremor. Conclusion. New derivatives of tietan-1,1-dioxide possess properties, which are inherent to antidepressants, and may be recommended for further in-depth study of their antidepressant activity.

anti-depressant activity, tietan-1, 1-dioxides, neuropharmacological interaction