The antihypertensive effects of methyldopa and clonidine result from agonist activity at alpha adrenoceptor sites within the brain. Methyldopa is converted enzymatically to alpha-methylnoradrenaline in noradrenergic neurones in rat brain and replaces the natural transmitter, noradrenaline. Radioligand receptor studies show that alpha-methylnoradrenaline differs from noradrenaline in being much more selective (70 times) for the alpha2 subclass of adrenoceptors than noradrenaline and it is likely that the antihypertensive action of methyldopa results from selective activation of alpha2 adrenoceptors by alpha-methylnoradrenaline in the nucleus tractus solitarius and the anterior hypothalamus. Radioligand studies also show that clonidine is a selective alpha2 adrenoceptor agonist although it probably interacts with alpha] adrenoceptors at higher concentrations. With regard to a withdrawal syndrome after cessation of clonidine treatment, the cardiovascular and behavioural components can now be characterised in a rat model. The components include increases in basal blood pressure and heart rate, as well as increases in cardiovascular reactivity and also increases in rapid eye movement (REM) sleep, body shakes and tremor which is reminiscent of an opiate withdrawal syndrome. Increased central noradrenergic activity is involved in this syndrome and alpha1 and alpha2 adrenoceptors mediate opposing effects on the REM sleep rebound component.
|Number of pages||14|
|Journal||Clinical and Experimental Hypertension. Part A: Theory and Practice|
|Publication status||Published - 1 Jan 1984|
- Blood pressure
- Central alpha adrenoceptors