Comparative evaluation of the Ca2+-antagonistic activity of some Bulgarian vasodilating agents and of known Ca2+-antagonists on K+-depolarized smooth muscle from guinea-pig taenia coli.
The informative value of the experimental model for inhibition of the effect of the Ca2+-induced contraction in 40 mM K+-depolarized smooth muscle from guinea-pig taenia coli, is investigated in order to determine the intensity of the Ca2+-antagonistic activity of different agents on the voltage-dependent calcium channels. The Ca2+-antagonistic activity of two original Bulgarian vasodilating agents - piperazine derivatives (aligeron and P-11) possessing potential Ca2+-blocking properties, is compared with the activity of known Ca2+-antagonists which are widely used in clinical practice (verapamil, nitrendipine, cinnarizine and flunarizine). Cumulative dose-response curves of CaCl2 (0.1-3.0 mM) in Ca2+ free K+-depolarizing solution are recorded in advance and 30 min after the administration of the test-substances. On the basis of the intensity of the Ca2+-antagonistic activity, determined by their pA2 values, the substances investigated are ordered as follows: nitrendipine greater than verapamil greater than cinnarizine greater than or equal to flunarizine greater than aligeron greater than P-11. On the background of the CaCl2-induced (1 mM) long-lasting contraction, the substances tested manifest qualitatively different relaxing effects, which suggest different mechanisms of action of the Ca2+ antagonists studied, as well as the significance of the experimental protocol in evaluating the intensity of the Ca2+ antagonistic activity.
Mutafova-Yambolieva
V
V
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Staneva-Stoytcheva
D
D
Nikolov
R
R
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002936:Cinnarizine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D005444:Flunarizine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D002936:Cinnarizine; D005444:Flunarizine; D011188:Potassium; D002118:Calcium