Functional characterization of central alpha-adrenoceptors by yohimbine diastereomers.

Rat occipital cortex slices were preincubated with [3H]noradrenaline and then superfused with medium containing 30 micrometer cocaine. They were stimulated electrically at 3 Hz. Unlabelled noradrenaline (0.1 micrometer), alpha-methyl-noradrenaline (0.01-0.1 micrometer), xylazine (0.1-10 micrometer) and guanabenz (0.01 micrometer) decreased, whereas yohimbine (0.01-1 micrometer), rauwolscine (0.01-1 micrometer), corynanthine (10 micrometers), tolazoline (0.1-10 micrometers) and azapetine (0.1-1 micrometer) increased the stimulation-evoked overflow of tritium without a change in basal outflow. Pseudoyohimbine and prazosin at up to 0.1 micrometer did not change the evoked overflow, and a higher concentrations enhanced the basal outflow of tritium. In vivo, yohimbine 10 mg/kg and rauwolscine 10 mg/kg markedly, and corynanthine 10 mg/kg slightly accelerated the alpha-methyltyrosine-induced disappearance of noradrenaline from rat whole brain. Yohimbine and rauwolscine but not corynanthine also accelerated the alpha-methyltyrosine-induced depletion of dopamine. The results add four compounds to the list of drugs with alpha-adrenoceptor affinity which inhibit (agonists) or facilitate (antagonists) action-potential-evoked release of noradrenaline in rat brain cortex. The presynaptic receptors are of the alpha 2-type. The receptors which control the activity of noradrenaline and dopamine neurons in vivo also appear to be alpha 2.