Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction

Abstract

Biochemical properties of 3-substituted 1,4-benzodiazepine determined by the characteristics of their chemical structure. Influence of 3-substituted 1,4-benzodiazepin-2-ones on maximal normalized rate and amplitudes of isometric smooth muscle contraction in rats was investigated. Compounds MX-1775 and MX-1828 demonstrated the similar inhibition effect on bradykinin-induced contraction of smooth muscle like competitive inhibitor des-arg9-bradykinin-acetate to bradykinin B2-receptors. MX-1626 demonstrated unidirectional changes of maximal normalized rate and force of smooth muscle that proportionally depended on bradykinin concentration in the range 10-10-10-6 M. MX-1828 has statistically significant decrease of normalized rate of smooth muscle contraction for bradykinin concentrations 10-10 and 10-9 M by 20.7 and 8.6%, respectively, but for agonist concentration 10-6 M, this parameter increased by 10.7% and amplitude was reduced by 29.5%. Compounds MX-2011, MX-1785 and MX-2004 showed no natural effect on bradykinin-induced smooth muscle contraction. Compounds MX-1775, MX-1828, MX-1626 were selected for further research of their influence on kinin-kallikrein system and pain perception.

Keywords

• 3-substituted 1_4-benzodiazepin-2-ones
• bradykinin
• force of contracti
• maximal normalized rate