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 micromol ml-1. Their inhibitory activities were not antagonized by alpha- or beta-adrenoceptor blockers but significantly reversed by CaCl2(0.015 micromol 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 beta2-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.
Bakheet
D M
DM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
El Tahir
K E
KE
Al-Sayed
M I
MI
El-Obeid
H A
HA
Al-Rashood
K A
KA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001767:Blinking / Q000187:drug effects; D002122:Calcium Chloride / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010120:Oxytocics / Q000494:pharmacology; D010121:Oxytocin / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004983:Ethanolamines; C120418:N-benzyl-1,2-diphenylethanolamine; C120417:N-ethyl-1,2-diphenylethanolamine; D010120:Oxytocics; D010276:Parasympatholytics; D014665:Vasodilator Agents; D010121:Oxytocin; D015232:Dinoprostone; D002122:Calcium Chloride; D011188:Potassium; D011224:Prazosin