EFFECT OF SALBUTAMOL AND THE PDE-INHIBITOR RA-642 ON THE CLONIDINE WITHDRAWAL SYNDROME IN RATS

: The effect of continuous subcutaneous infusion of clonidine and the influence of concomitant treatment with salbutamol as well as the acute effects of the PDE-inhibitor RA 642 on heart rate and blood pressure of conscious normotensive rats were studied. The severity of the cardiovascular clonidine withdrawal symptoms was positively related to the amount of clonidine infused during treatment. Concomitant infusion of salbutamol (12 mg/kg/day) and clonidine (300 microgram/kg/day) attenuated the clonidine withdrawal tachycardia in conscious normotensive rats. No difference existed in the isoprenaline induced tachycardia in pithed normotensive rats, 8-14 h after cessation of infusion with clonidine (300 microgram/kg/day) and saline, clonidine and salbutamol (12 mg/kg/day), or saline alone. The PDE-inhibitor RA 642 (12 mg/kg, i.p.) aggravated the clonidine withdrawal syndrome in conscious normotensive rats. These data may indicate that long-term treatment with clonidine induces a hyperactivation of the adenylate-cyclase/cAMP-system.