L.P. Kozaeva, E.P. Kramarova, A.I. Dovgii, V.G. Pukhalskaya

In the present paper, neurotransmitter activity of new derivative of N-methyl-N-[1-(3',7?,10?-trimethylsilatran-1-yl)¬methyl]acetamide (Sil-1) is reported. In vivo experiments were carried out on white male mice. The oral and intraperitoneal administration of silatrane increases peristaltic activity in the gastrointestinal tract and leds to diarrhea. Effects of the diarrhea increased in severity along with the doses. The cause of death in mice in all cases was colon bleeding. The results of acute single dose toxicity studies show that oral and intraperitoneal administration in mice exhibit a very low toxicity (LD50 values of intraperitoneal injections of Sil-1 was estimated as 2000 mg kg-1). The direct effects of compound were determined in vitro using isolated segments of guinea pig ileum, trachea and right atria. The natural full muscarinic agonist, acetylcholine (ACh), was used as reference. Sil-1 and ACh contracted the preparation of ileum and trachea in a dose-dependent manner. Both the maximal response evoked by Sil-1 and the EC50 were significantly lower, then equal measures of ACh in the some experiments. The increase of intestinal transit by Sil -1 as well as contractions of ileum and trachea segments were blocked by atropine (muscarinic antagonist). The protective effect of atropine indicates that the effects of silatrane are mediated by muscarinic receptor. Silatran almost was not effective on the spontaneous rate of isolated right atria, while ACh completely suppressed right atria contractions (3´10-6М). The present results demonstrate that a new organosilicon compound - N-(silatranylmethyl)acetamide has parasympathomimetic activity and it is a partial agonist of muscarinic receptors. The new silatran has more affinity to M3 - muscarinic receptors, than to M2 - muscarinic receptors. The new silatran posseses low toxicity and high efficiency.