Guanidines as analogs of histamine and antihistamines on the isolated guinea-pig ileum.
The present work describes the interaction of phenylguanidine and cyclohexylguanidine with receptor structures of the isolated guinea-pig ileum. It is suggested that phenylguanidine in the range of 0.2-2 mM, acts in a way similar to histamine. At lower concentrations in the bath, phenylguanidine and cyclohexylguanidine, behave as competitive antagonists of histamine, with Ki values close to 0.1 mM and 0.4 mM, respectively. At higher concentrations phenylguanidine acts as agonist with a Kn near 0.3 mM; the Kn for histamine was found to be 0.127 muM, in agreement with previous data from the literature. The agonistic action of phenylguanidine is inhibited by promethazine and atropine, which have Ki values of 0.342 muM and 0.575 muM, respectively. Cyclohexylguanidine is devoid of spasmogenic activity, and this was attributed to the lack of aromatic character and to the bulkiness of the cyclohexyl side chain.
D000818:Animals; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000031:analogs & derivatives*; D006633:Histamine Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D011968:Receptors, Histamine / Q000187:drug effects
D006146:Guanidines; D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine