STUDIES ON THE SPASMOLYTIC AND UTERINE RELAXANT ACTIONS OF N -ETHYL AND N -BENZYL-1,2-DIPHENYL ETHANOLAMINES: ELUCIDATION OF THE MECHANISMS OF ACTION

The influence of N -ethyl- and N -benzyl-1,2-diphenyl ethanolamines (compounds E and B, respectively) was examined on the spontaneously contracting rabbit jejunum and the rat uterus together with their influence on the contractions induced by some spasmogens in the guinea-pig ileum and oxytocics and CaCl₂in the pregnant rat uterus. Both E and B inhibited the spontaneous contractions of the rabbit jejunum with ID₅₀values of 0.13 and 0.03 μmol ml⁻¹. Their inhibitory activities were not antagonized by α- or β-adrenoceptor blockers but significantly reversed by CaCl₂(0.015 μmol ml⁻¹). The compounds also antagonized nicotine, ACh-, histamine-, 5-HT- and CaCl₂-induced contractions by 44–100%. Compound E seemed to be several times more potent than B in inhibiting the spontaneous uterine contractions with an ID₅₀of (7 nmol ml⁻¹). Their inhibitory effects were not antagonized by β₂-adrenoceptor or H₂-receptor blocking drugs. Both compounds (40 nmol ml⁻¹) antagonized in a competitive manner CaCl₂-induced contractions in the K⁺-depolarised uterus and PGE₂and oxytocin-induced uterine contractions. The ID₅₀values were in the range of 1.6–10.7 nmol ml⁻¹. The results suggest that E and B compounds may be considered as putative L-Ca²⁺channel blockers with certain selectivities. The E compound seemed to be more selective against uterine L-Ca²⁺channels and the B compound against intestinal smooth muscles. Thus, the compounds may be of potential value in treatment of some colics, the irritant bowel syndrome, dysmenorrhoea and premature deliveries. 1999 Academic Press@p$hr