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The effect of the alpha 2-adrenoceptor agonist clonidine on plasma free MHPG levels was assessed in 12 normal volunteers. A significant fall in MHPG was produced by 1.5 microgram X kg-1 clonidine IV whereas saline had no effect. The peak fall in MHPG correlated strongly with the area under the curve (AUC). In addition, a strong correlation was seen between basal MHPG and the extent of the clonidine-induced fall. This suggests that plasma MHPG levels are not simply a reflection of central alpha 2-adrenoceptor function and argues against tonic alpha 2-adrenoceptor-mediated inhibitory control of noradrenergic output.

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Central alpha-2-adrenoceptor function was studied in seven withdrawing alcoholics and compared with seven normal controls using the clonidine challenge test. The alcoholic group had significantly elevated basal levels of blood pressure and plasma 3-methoxy-4-hydroxy-phenyl glycol. The percentage of fall in blood pressure produced by clonidine was blunted in the alcoholics. There was disruption of the neuroendocrine effects of clonidine on growth hormone release. Physiological indices of withdrawal, in particular plasma 3-methoxy-4-hydroxyphenyl glycol and blood pressure correlated with measures of previous withdrawal experiences, supporting the idea that kindling might occur with repeated episodes of withdrawal.