Inhibition of tetrahydroisoxazolo-pyridin-3-ol and muscimol and its mechanism on gastrointestinal transit in mice.

The effect of tetrahydroisoxazolo-pyridin-3-ol (THIP) and muscimol on gastrointestinal transit and a possible mechanism for this effect were studied using the charcoal meal test in mice. These agents inhibited transit dose relatedly. The inhibitory effect was completely reversed by yohimbine and phentolamine. A minor degree of antagonism by bicuculline was observed. There were an additive response in morphine-pretreated animals and partial antagonism in naloxone-pretreated animals. Propranolol failed to modify the inhibitory effect. The findings suggest a predominantly alpha 2-receptor-mediated inhibitory effect on gastrointestinal transit for THIP and muscimol which possibly also utilizes opioid pathways. However, it appears that beta-adrenergic and GABAergic systems might not contribute to this effect.