Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity

Phenoxybenzamine, but not phentolamine or propranolol, blocked central noradrenaline receptors in flexor reflex experiments on the rat spinal cord using the selective noradrenaline receptor stimulating agent clonidine. None of these three drugs blocked dopamine receptors in experiments on turning of unilaterally striatectomized rats induced by the dopamine receptor stimulating agent apomorphine. The -methyltyrosine-induced disappearance of noradrenaline in the central nervous system of rats and mice was accelerated by phenoxybenzamine at doses related to the functional changes, whereas the other drugs were inefficient. The disappearance of dopamine was decelerated by phenoxybenzamine, but not by phentolamine or propranolol.The effects of the adrenergic receptor blocking agents on motor activity were studied in a model in which clonidine potentiated the activation induced by apomorphine in reserpine-treated mice. Phentolamine (20 mg/kg) and propranolol (10 mg/kg) reduced the stimulation seen both after apomorphine alone and in combination with clonidine, indicating nonspecific sedative effects. Phentolamine (10 mg/kg) blocked the peripheral effects of clonidine but did not markedly diminish the activation induced by the receptor stimulants. Phenoxybenzamine (20 mg/kg) blocked the clonidine-induced potentiation without interfering with the apomorphine-induced stimulation and can thus be used as a blocking agent of central and peripheral noradrenaline receptors in behavioural experiments.