We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor ligands), and oxybutynin (a currently used anti-pollakiuria drug) on cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared to sham-treated rats, acetone-treated cystitis models exhibited an increase in urinary frequency during continuous filling cystometry. Intravenous administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with cystitis dose-dependently prolonged micturition intervals and increased the micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended micturition intervals, but decreased the micturition pressure. These results indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent urination caused by acetone-induced cystitis in a manner different from that of oxybutynin.

2001-01-01·European Journal of Pharmacology3区 · 医学

Pharmacological actions of AH-9700 on micturition reflex in anesthetized rats

3区 · 医学

Article

作者: Seiko Oku ; Isao Shimizu ; Daisuke Ishii ; Makoto Oka ; Katsuyoshi Kawashima ; Hitoshi Kohayakawa

In radioligand binding assays, AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2-naphthalenyl)ethyl]pyrrolidine fumarate) had high affinity for sigma receptors and moderate affinity for muscarinic receptors. The affinity of AH-9700 for sigma(1) receptors was significantly reduced in the presence of 5'-guanylyl-imidodiphosphate (GppNHp). In isolated bladder strips of rats, AH-9700 inhibited carbachol-induced contractions. In anesthetized rats, i.v. administration of AH-9700 and typical sigma receptor ligands, (+)-pentazocine and 1,3-di-o-tolylguanidine (DTG), but not oxybutynin, dose-dependently inhibited rhythmic isovolumetric reflex bladder contractions. AH-9700 and oxybutynin suppressed the amplitude of rhythmic bladder contractions. On the other hand, at doses lower than used i.v., the i.c.v. administration of AH-9700 or the sigma receptor ligands inhibited rhythmic bladder contractions without suppressing the amplitude. This inhibitory effect of AH-9700 was markedly reduced by pretreatment with i.c.v. pertussis toxin. These results suggest that AH-9700 exerts a marked anti-micturition reflex effect through central sigma receptors possibly related to pertussis toxin-sensitive Gi/o-proteins and a moderate spasmolytic effect based on its peripheral anti-muscarinic activity.

100 项与 AH-9700 相关的药物交易

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