The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations

SUMMARY The activities of menthol and peppermint oil were determined in guinea‐pig ileal smooth muscle, in rat and guinea‐pig atrial and papillary muscle, in rat brain synaptosomes and in chick retinal neurones by pharmacological 45Ca2+ uptake and radioligand binding assays. Menthol is a major constituent of peppermint oil and is approximately twice as potent as peppermint oil as an inhibitor of K+ depolarization‐induced and electrically stimulated responses in ileum and electrically stimulated atrial and papillary muscles. IC50 values in the ileal preparation ranged from 7.7 to 28.1 μg ml−1 and in the cardiac preparations from 10.1 to 68.5 μg ml−1. Similar potencies were demonstrated against K+ depolarization‐induced 45Ca2+ uptake in synaptosomes and against K+ depolarization and Bay K 8644‐induced uptake in chick retinal neurons. IC50 values for menthol inhibition of K+ and Bay K 8644 responses in the retinal neurons were 1.1 × 10−4 M (17.2 μg ml−1) and 1.75 × 10−4 M (26.6 μg ml−I), respectively, and for peppermint oil were 20.3 and 41.7 μg ml−1 respectively. Both menthol and peppermint oil inhibited specific [3H]nitrendipine and [3H]PN 200–110 binding to smooth and cardiac muscle and neuronal preparations with potencies comparable to, but slightly lower than, those measured in the pharmacological and 45Ca2+ uptake experiments. Binding of menthol and peppermint oil, studied at 78 μg ml−1, was competitive against [3H]nitrendipine in both smooth muscle and synaptosome preparations. The data indicate that both menthol and peppermint oil exert Ca2+ channel blocking properties which may underlie their use in irritable bowel syndrome. Ca2+ channel antagonism may not be the only pharmacological effect of menthol and peppermint oil contributing to intestinal smooth muscle relaxation.