Antihistaminic properties of AF-14, an experimental quinuclidine derivative: discrimination between two histaminergic sites in both guinea-pig ileum and bladder.
AF-14 (1-aza-4-phenyltricyclo[6.2.2.0(2,7)]dodecan-5-one), a selective antimuscarinic agent, was shown to block the histamine-induced contractile response in Krebs solution in guinea-pig ileum and bladder. Careful linear regression analyses of the concentration-response relationship revealed that AF-14 antagonism consisted of two sequential and distinct phases, corresponding to an early phase and a late phase of the contractile response to histamine. In the late phase, the action of AF-14 was consistent with competitive antagonism, its pA2 (95% confidence limits) being 5.80-6.06 (ileum) and 5.66-5.80 (bladder). In the early phase, AF-14 almost completely blocked the contractile response at a concentration of 100-300 nM, which was much less than required to block the late phase or cholinergic contractions of the ileum or bladder. It is concluded that AF-14 discriminates between two histamine-sensitive sites that mediate muscle contraction in each of the two organs.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D009388:Neostigmine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D011968:Receptors, Histamine / Q000187:drug effects*; D001743:Urinary Bladder / Q000378:metabolism
D010276:Parasympatholytics; D011812:Quinuclidines; D011968:Receptors, Histamine; D009388:Neostigmine; C047132:AF 14; D001285:Atropine; D006632:Histamine