title: Effects of the optical isomers of a novel 5-HT2 antagonist and (-)-Bay K 8644 on spontaneous mechanical activity in rat portal veins.
abstract: The effect of the (+)-enantiomer (Ir) and the (-)-enantiomer (Lu) of a novel 5-HT2 antagonist was studied on spontaneous mechanical activity in rat portal veins and compared to that of the Ca-agonist (-)-Bay K 8644. Ir and Lu (10(-8) to 10(-5) M) were found to equally increase the spontaneous mechanical activity in rat portal veins. At high concentrations (10(-4) M) Ir and Lu totally abolished spontaneous activity. The frequency of the spontaneous activity was equally decreased by the two enantiomers. The increase in spontaneous activity induced by Ir and Lu was abolished in Ca-free medium and restored by readdition of Ca. The augmenting effect of the enantiomers on mechanical activity was not influenced by atropine but was totally eliminated by the Ca-antagonist nifedipine. The Ca-agonist (-)-Bay K 8644 was more potent in increasing the amplitude of the mechanical activity than the enantiomers and had a concentration-dependent increasing effect on the frequency of the spontaneous activity. The results indicate that in rat portal veins Ir and Lu have a dual non-stereoselective effect which may include a Ca-agonistic stimulating mechanism of action as well as a pacemaker blocking effect.
authors.affiliation: Institute of Pharmacology, University of Arhus, Denmark.
authors.forename: E O
authors.initials: EO
authors.lastname: Mikkelsen
authors.forename: T J
authors.initials: TJ
authors.lastname: Nielsen
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D007093:Imidazoles; D010879:Piperazines; D012702:Serotonin Antagonists; C056634:irindalone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester