Cardiovascular action of detomidine, a sedative and analgesic imidazole derivative with alpha-agonistic properties.

The cardiovascular effects of detomidine, a new veterinary sedative and analgesic imidazole derivative were studied in rats and cats using as reference compound xylazine, a widely employed veterinary antinociceptive and sedative drug with alpha-agonistic potency. Detomidine (1-30 micrograms/kg i.v.) and xylazine (10-1000 micrograms/kg i.v.) had both dose-dependent hypotensive and bradycardiac effects in anaesthetized rats. After i.v. administration of 3-100 micrograms/kg detomidine and 0.1-3 mg/kg xylazine to conscious rats, detomidine was more active in reducing the heart rate than in lowering the blood pressure. In anaesthetized cats, detomidine (1-30 micrograms/kg i.v.) was hypotensive and bradycardiac in a dose-dependent manner. A low dose of detomidine into the vertebral artery was more effective than i.v. application in reducing blood pressure. Idazoxan (0.3 mg/kg i.v. and 0.03 mg/kg into the vertebral artery) antagonized the hypotensive and bradycardiac effects of detomidine injected into the femoral vein or vertebral artery, respectively. In pithed rats, detomidine and xylazine stimulated presynaptic and postsynaptic alpha 2-adrenoceptors, and to a lesser extent postsynaptic alpha 1-adrenoceptors. The results indicate that detomidine is an agonist of central and peripheral alpha 2-adrenoceptors which exerts its hypotensive and bradycardiac effects via activation of the central alpha 2-adrenoceptors.