title: Stereo-selective calcium antagonistic and binding properties of the enantiomers of lemildipine in vascular tissue of pigs and dogs.
abstract: Stereo-selective calcium antagonistic properties of the enantiomers of lemildipine (CAS 94739-29-4, NB-818) were assessed in vascular tissues, including pig coronary artery and dog cerebral artery. Ca2+ antagonistic action of (-)-lemildipine was about 5 times and 100 times more potent than nifedipine and (+)-lemildipine, respectively. (-), (+), and (+/-)-lemildipine showed a slow onset and long duration of Ca2+ antagonistic action. Pretreatment with (-)-lemildipine and (+/-)-lemildipine for 30 min inhibited the contractions produced by 5-hydroxytryptamine and endothelin-1 with pD2 values between 6.0-8.5, whereas (+)-lemildipine and nifedipine were less potent. Of the lemildipine enantiomers, (+)-lemildipine at a low concentration (1 nmol/l) had a slight but significant Ca2+ agonistic action. However, (+)-lemildipine had no apparent effect on the pCa-tension relationship in the dog basilar artery permeabilized with Staphylococcus aureus alpha-toxin. Enantiomers of lemildipine as well as nifedipine competitively antagonized the specific binding of (+)-[3H]PN 200-110 (isradipine) to the membranes of pig coronary artery in the following order: (-)-lemildipine > nifedipine > (+/-)-lemildipine > (+)-lemildipine. These results suggest that the stereo-selective Ca2+ antagonistic actions of lemildipine enantiomers and nifedipine assessed in the functional experiments were well correlated with their potencies for the competition with the (+)-[3H]PN 200-110 binding to the pig coronary artery.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuta
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004095:Dihydropyridines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D013237:Stereoisomerism; D013552:Swine; D010738:Type C Phospholipases / Q000494:pharmacology
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011189:Potassium Chloride; C048962:NPK 1886; D010738:Type C Phospholipases; D002118:Calcium