On the assessment of the potency of antagonists using the rat isolated anococcygeus muscle.
The conditions required for assessing the potencies of antagonists of muscarinic and at alpha-adrenoceptors have been examined using contractility studies with the rat anococcygeus muscle. Physostigmine (5 X 10(-7) M) and atropine (10(-8)-10(-7) M) had no effect on the responses to noradrenaline. The responses to acetylcholine were potentiated by physostigmine and inhibited by atropine. Physostigmine and atropine increased the slopes of the concentration-response curves to acetylcholine. In the presence of physostigmine, atropine at 10(-8) M inhibited the responses without altering the slopes of the concentration-response curves to acetylcholine. The responses to acetylcholine were potentiated by cocaine (greater than 10(-6) M) and inhibited by phentolamine (10(-6) M). Cocaine (10(-6) - 5 X 10(-6) M) potentiated and phentolamine (10(-7) - 10(-6) M) inhibited the responses to noradrenaline. The slopes of the concentration-response curves to noradrenaline were increased by cocaine at 5 X 10(-6) M, but not at 10(-6) - 2 X 10(-6) M, and by phentolamine. In the presence of cocaine (10(-6) M), phentolamine (10(-7) - 5 X 10(-7) M) inhibited the responses and increased the slopes of the concentration-response curves to noradrenaline. These results illustrate that, in the rat anococcygeus muscle, it is possible to assess the potency of muscarinic antagonists with the method described. However, in this tissue, alpha-adrenoceptor blocking activity cannot be determined with noradrenaline as the agonist in the presence of cocaine.
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D011976:Receptors, Muscarinic; D001285:Atropine; D010830:Physostigmine; D003042:Cocaine; D000109:Acetylcholine; D009638:Norepinephrine; D010646:Phentolamine