Antihistaminic activity of carane derivatives in isolated guinea pig ileum.

Local anesthetics (LAs) inhibit membrane depolarization by reducing sodium and potassium conductance, and subsequent displacement of calcium ions from binding sites seems to occur. Histamine release appears to be a secretory process in which calcium couples the stimulus to the exocytosis of histamine-containing granules. Furthermore, LAs are structurally similar to histamine H(1)-receptor antagonists. Thus, LAs can be considered antihistaminic drugs. Previous pharmacological investigations have shown strong local anesthetic, anti-inflammatory and analgesic activity of the carane derivative KP-23. As it has previously been demonstrated that KP-23R,S and its R,S-diasteroisomers have an inhibitory effect on guinea pig ileum contractions, the aim of the present study was to determine and compare the antihistaminic effects of KP-23R,S and its individual isomers KP-23R and KP-23S on isolated guinea pig ileum.