5-HT3 receptor blocking properties of the antiparkinsonian agent, talipexole.
1. Talipexole showed moderate displacement activity of 3H-GR 65630 binding to 5-HT3 receptors in both rat cortical and intestinal membrane fractions with Ki values of 0.35 microM and 0.22 microM, respectively. 2. Bromocriptine failed to displace the binding activity in either experimental system even at a concentration of 10 microM. 3. Both talipexole and tropisetron were found to significantly inhibit 5-HT3 receptor-mediated effects of 5-HT in isolated guinea-pig ileum or atrium; however, the effect of talipexole was weaker than that of tropisetron. 4. Bromocriptine, in contrast, had no antagonistic effects on 5-HT3 receptor-mediated activity in guinea-pig ileum or atrium. 5. It was concluded that talipexole might act as an antagonist on 5-HT3 receptors in both brain and intestinal tissues.
Nishio
H
H
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Kohno
Y
Y
Fujii
A
A
Negishi
Y
Y
Inoue
A
A
Nakata
Y
Y
D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004639:Emetics / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D007093:Imidazoles / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007211:Indoles / Q000493:pharmacokinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology
D001381:Azepines; D018492:Dopamine Antagonists; D004639:Emetics; D007093:Imidazoles; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C059068:GR 65630; D001971:Bromocriptine; C024763:talipexole