Effect of nizatidine and ranitidine on the D-tubocurarine neuromuscular blockade in the toad rectus abdominis muscle.
The influence of varying concentrations of the H2-receptor antagonists nizatidine and ranitidine on the acetylcholine- and carbachol-induced contractures on the toad rectus abdominis muscle, as well as the possible interaction between the above H2-receptor antagonists and D-tubocurarine were studied. Nizatidine and ranitidine at a concentration of 3.2 x 10(-4) mol l-1 augmented, and at 3.2 x 10(-3) mol l-1 inhibited, the acetylcholine-induced contractures on the toad rectus abdominis muscle, while at concentrations from 3.2 x 10(-4) to 3.2 x 10(-3) mol l-1 they inhibited the carbachol-induced contractures, in a concentration-dependent manner. In addition, nizatidine and ranitidine at a concentration of 3.2 x 10(-4) mol l-1 reversed the D-tubocurarine blocking activity on the acetylcholine-induced contractures, but at a concentration of 3.2 x 10(-3) mol l-1 they augmented it. These findings provide evidence that the above H2-receptor antagonists produce either cholinesterase inhibition or neuromuscular blockade, depending on their concentration. Thus, the D-tubocurarine neuromuscular blocking activity is potentiated at high concentrations of nizatidine and ranitidine, while it is reversed at lower ones.
Kounenis
G
G
Department of Pharmacology, Faculty of Veterinary Medicine, Aristotelian University, Thessaloniki, Greece.
Koutsoviti-Papadopoulou
M
M
Elezoglou
V
V
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002025:Bufonidae; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D006635:Histamine H2 Antagonists / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016567:Nizatidine / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*; D017568:Rectus Abdominis / Q000187:drug effects*; D014403:Tubocurarine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D003473:Neuromuscular Nondepolarizing Agents; D011899:Ranitidine; D002217:Carbachol; D000109:Acetylcholine; D016567:Nizatidine; D014403:Tubocurarine