[Effect of beta 2-adrenergic agonists on neurotoxic action of aminophyllines]

The purpose of the present investigation was to evaluate whether the beta 2-adrenergic agonists affect the pharmacodynamics and pharmacokinetics of aminophylline-induced seizures. Adult male Albino Swiss mice were treated i.p. with salbutamol, fenoterol or terbutaline and 30 min. later they received i.p.aminophylline. During 90 min. observation clonic and tonic seizures and also mortality of mice were registered. Moreover the influence of beta 2-adrenomimetics on electroshock-induced seizure threshold (CS 50) and on plasma aminophylline concentration was estimated. It was found that pretreatment with salbutamol, fenoterol and terbutaline decreased the ED 50 (for clonic and tonic seizures) and LD 50 of aminophylline. Fenoterol decreased but terbutaline increased the CS 50 in mice. Only terbutaline elevated significantly the plasma concentration of aminophylline. The data indicate that concomitant treatment with beta 2-adrenergic agonists together with aminophylline increase the risk of aminophylline-induced seizures. Thus plasma monitoring of aminophylline concentration could be used in all patients treated simultaneously with beta-2-adrenergic agonists and aminophylline.