No abstract

Local Anaesthetic Activity of 1,2-Disubstituted Imidazo[1,2-a]benzimidazoles. -A series of new 1-dialkylaminoalkylimidazobenzimidazoles (VII) (11 examples) are synthesized, of which the majority displays marked local anaesthetic activity. Derivatives (VIIc) and (VIIe) appear to be the most active ones. -(ANISIMOVA, V. A.; OSIPOVA, M. M.; GALENKO-YAROSHEVSKII, A. P.; PONOMAREV, V. V.; POPKOV, V. L.; PRIKHOD'KO, A. K.; KADE, E. A.; SPASOV, A. A.; Khim.-Farm. Zh. 36 (2002) 8, 21-24; Nauchno-issled. inst. fiz. org. khim., Rostov. gos. univ., Rostov-na-Donu 344090, Russia; Russ.) -Koehler 03-103

We studied kinetic parameters of interaction of local anesthetics (lidocaine, tetracaine, bupivacaine, and two novel agents with proved local anesthetic potency RU-353 and RU-1117) with human serum albumin. Complexation of local anesthetics with human serum albumin is a time-dependent and reversible process; equilibrium was attained within 1.5-4.5 h depending on chemical nature of local anesthetics.

We compared the effects of local anesthetics procaine, amethocaine (dicaine), bupivacaine, and a new agent RU-1148 on hydrolytic activity of human plasma butyrylcholinesterase. The butyrylcholinesterase-blocking activity of the test substances decreased in the following order: bupivacaine>amethocaine>procaine>RU-1148. The study of the capacity of these agents to form complexes with human plasma proteins and serum albumin showed that RU-1148 in therapeutic concentrations was transported by human serum albumin,beta-globulin, and acid glycoproteins. Study of the mechanisms of pharmacodynamic interactions between clonidine and RU-1148 demonstrated good prospects of their combined use.

We studied the mechanisms of combined action of clonidine and local anesthetics amethocaine and imidazo-benzimidazole derivative RU-1117. In contrast to amethocaine, RU-1117 in therapeutic concentrations binds to imidazoline receptors and, to a lesser extent, to alpha(2A)-adrenoceptors on human platelets. Clonidine and RU-1117 produce opposite effects on platelet aggregation induced by ADP in low concentrations. Our results suggest that the pharmacodynamic interaction of clonidine and RU-1117 is associated with their ability to activate the imidazolinergic system.