The colonic prokinetic activity of a newly synthesized compound, T-1815, administered orally, was compared with that of yohimbine and naloxone in mice. The time required to evacuate a glass bead inserted into the distal colon was taken as an index of prokinetic activity. Clonidine (3-30 μg/kg s.c.), and loperamide (0.3-3.0 mg/kg s.c.) delayed bead expulsion in a dose-dependent manner. Yohimbine (0.3-10 mg/kg) and T-1815 (0.1-10 mg/ kg) showed a dose-dependent reduction of the delay in evacuation induced by clonidine, but naloxone had no effect. The loperamide-induced retardation of colonic propulsion was reduced by naloxone (0.3-10 mg/kg) and T-1815 (0.1-10 mg/kg) in a dose-dependent manner, but yohimbine had no effect. In normal animals, yohimbine and naloxone had no significant effect on evacuation, while a slight acceleration was observed with T-1815 at 10 mg/kg. No soft feces and/or diarrhea were observed with any of the three test drugs. These results indicate that T-1815 appears to be a unique colonic prokinetic compound, the action of which may be mediated through mechanisms other than antagonism for α2-adrenoceptors or opioid receptors.

抄録全体を表示

Instillation of pilocarpine-induced a miosis in a rabbit. In an isolated iris sphincter muscle of rabbit, pilocarpine induced a small contraction and behaved as an antagonist of carbachol. The contractile response of an isolated rabbit dilator muscle to a field stimulation was inhibited by pilocarpine. This inhibitory action of pilocarpine was antagonized by atropine in a concentration-dependent manner. An amount of norepinephrine released from the electrically stimulated dilator muscle was inhibited by pilocarpine. The inhibitory effect of pilocarpine on norepinephrine release was decreased by atropine. A following explanation is proposed as a most possible mechanism for the pilocarpine-induced miosis in the rabbit. Pilocarpine activates the prejunctional cholinoceptors to inhibit norepinephrine release from the adrenergic nerve in the dilator muscle. Thus pilocarpine decreases tonus of the dilator muscle and induces the miosis.

抄録全体を表示

The affinities of various muscarinic antagonists to human detrusor muscle were determined using radioligand binding techiniques. Saturation experiments with ³H-QNB revealed that there were significant amount of muscarinic cholinergic receptors in human detrusor muscle. Displacement of ³H-QNB binding by various muscarinic subtype selective drugs was studied in the inhibition experiment. Pirenzepine, AFDX-116 and 4-DAMP inhibited the ³H-QNB binding to human detrusor muscle with the Ki values (nM) (mean±S. D., n=6) of 243±62.5, 59.7±15.3 and 2.69±0.96, respectively. These data indicate that M3-selective drug possesses the highest affinity to human detrusor muscle. The Ki values of oxybutynin and tiquizium bromide were similar to those of 4-DAMP, suggesting that these two drugs have strong affinities to human detrusor muscle.

抄録全体を表示