Attempt at pharmacological differentiation of central beta-adrenergic receptors.

The beta-adrenergic stimulants isoprenaline, salbutamol and clenbuterol decreased motor activity, reduced the interest of fasting mice in food pellets ('Tantale' test), and antagonized high-dose apomorphine hypothermia. Clenbuterol was 16--60 times more potent than the other two agonists in all tests, apparently because of better crossing into the C.N.S. The beta-adrenergic blockers, d,l-propranolol and l-penbutolol, completely antagonized the effects of salbutamol and clenbuterol in tests of motor activity and apomorphine hypothermia, penbutolol being 30--60 times more active than propranolol, perhaps due to its greater lipid solubility. The Tantale test allows unambiguous differentiation between penbutolol and propranolol. While the first completely blocked the effects of clenbuterol and salbutamol, the second was effective only within a narrow dose range. Finally, the dose-effect relationships of the 3 agonists were parallel in the Tantale test, while they were divergent in the other two. This suggests that different classes of beta-adrenergic receptors may be involved in the various test.