THE EFFECT OF SOME α2‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE

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Abstract
SUMMARY: 1. The effects of graded doses of the α2‐adrenoceptor agonists clonidine, tizanidine and BHT‐920, and the α2‐adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test.2. The agonists produced significant and dose‐dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT‐920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg).3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co‐administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg).4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT‐920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg).5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline‐treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT‐920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.