Functional characterization of central α-adrenoceptors by yohimbine diastereomers

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