PHARMACOLOGICAL PROPERTIES OF KRYPTOPYRROLE AND ITS OXIDATION-PRODUCTS ON ISOLATED SCIATIC-NERVE OF RAT AND ON GUINEA-PIG ILEUM

Kryptopyrrôle (2, 4‐dimethyl, 3‐ethylpyrrôle) inhibited conduction in rat sciatic nerve by a local anaesthetic action. Tone and both spontaneous and electrically‐induced contractions of guinea‐pig ileum were also inhibited by kryptopyrrôle. The concentration of kryptopyrrôle required for 50% inhibition of a maximum twitch tension (ID50) was 0.085 him. Oxidation products of kryptopyrrôle with chromatographic properties similar to those of urinary constituents reported in schizophrenia and hepatic porphyrias had little or no effect at similar concentrations. Dose‐response curves to exogenous acetylcholine in guinea‐pig ileum were shifted to the right by kryptopyrrôle, with loss of parallelism and reduction in the maximum contraction. Acetylcholine overflow from ileal segments at rest and during electrical stimulation was reduced by kryptopyrrôle. These results on ileal segments are consistent with kryptopyrrôle having both a post‐junctional site of action, presumably directly on the muscle, and a pre‐junctional site reducing the output of acetylcholine from the myenteric plexus. The significance of these findings is discussed in relation to a possible clinical pathological rôle for these compounds. 1979 British Pharmacological Society