Alpha-2-adrenergic agonists and imidazolines

Stimulation of postsynaptic alpha-2-adrenergic receptors induces vasoconstriction, but stimulation of presynaptic alpha-2-adrenergic receptors decreases norepinephrine release. Alpha-2-adrenergic agonists which cross easily the blood-brain barrier decrease norepinephrine release in brain, particularly in centers regulating arterial pressure. The stimulation of central alpha-2-adrenergic receptors decreases sympathetic tone and norepinephrine release by peripheral sympathetic terminations. Alpha-2-adrenergic agonists crossing the blood-brain barrier have an hypotensive effect and are called sympatholytic and centrally acting hypotensive drugs. The drug of reference in this group is alpha-methyldopa.

Moreover, the existence of receptors different from the alpha-2-adrenergic receptors, but having the same function as them for regulation of arterial pressure, has been shown. They are called imidazoline receptors because their agonists, drugs like clonidine and rilmenidine, have a chemical structure with an imidazole heterocycle.

The first two drugs used as centrally acting hypotensives were alpha-methyldopa and clonidine.

  • Alpha-methyldopa
    Alpha-methyldopa is converted to alpha-methyl-noradrenaline which activates central adrenergic alpha-2 receptors and decreases the sympathetic tone. It is indicated in the treatment of arterial hypertension. Alpha-methyldopa induces numerous adverse effects: hemolytic anemia, granulocytopenia, fever, hepatic damage. It can worsen a depressive state.
  • Clonidine
    Clonidine, which was classified among drugs stimulating alpha-2 adrenergic receptors, stimulates, in fact imidazoline receptors resulting in the same effect: decrease of arterial pressure. It has moreover sedative and anxiolytic actions and reinforces the analgesic effect of morphine and of general anesthetics.
    The other drugs of clonidine type, guanfacine, rilmenidine, moxonidine are also used in the treatment of arterial hypertension.
    These drugs, are likely to induce depressive states or to reveal latent depressive states. The antagonists of central presynaptic alpha-2 receptors have on the contrary an antidepressant effect. In addition, according to a clinical trial, the use of moxonidine is contra-indicated in patients with congestive heart failure.
    Abrupt discontinuation of alpha-2 agonists, in particular that of clonidine, can be followed by a rebound of arterial hypertension, tachycardia, sweats, and agitation. These disorders, which partly resemble that of morphine discontinuation, are suppressed by clonidine readministration. Clonidine can be used to reduce the intensity of symptoms of morphine withdrawal.


    CATAPRES* Tablets, TTS

  • Apraclonidine
    Apraclonidine,called also para-aminoclonidine, is an alpha-2 adrenergic agonist which is used in an ophthalmic solution for decreasing intraocular pressure, by reducing the formation of aqueous humor.
  • Brimonidine has properties quite similar to those of apraclonidine and is also used in ophthalmic solution in the treatment of glaucoma.


    ALPHAGAN* P Ophthalmic solution

  • Medetomidine and its enantiomer, dexmedetomidine, are classified among the most active alpha-2 adrenergic agonists.
    Tizanidine is an alpha-2 adrenergic agonist proposed for the treatment of the muscular hypertonicity of neurological origin; its mechanism of action in this therapeutic use remains to be elucidated.


    TIZANIDINE Tablets


Guanethidine is a drug which does not cross the blood-brain barrier but penetrates by active transport in peripheral adrenergic terminations where it takes noradrenaline's place and inhibits its release. Its effect is sometimes named sympathoplegic. It is not used any more in treatment of arterial hypertension because, in particular, of the orthostatic hypotension which it elicited. It was also marketed in the form of ophthalmic solution, in combination with adrenaline whose effects it reinforces, for treatment of chronic glaucoma.

Iobenguane is a derivative with a guanidine group and a phenyl group carrying a radioiodine atom. It is known as MIBG (meta-iodobenzylguanidine). It penetrates into the adrenergic terminations and is used in diagnosis and treatment of pheochromocytoma and neuroblastoma.
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Quizz : Q 119
Clonidine lowers blood pressure:
by inhibiting alpha-1 adrenergic receptors
by inhibiting angiotensin converting enzyme
by  stimulating central alpha-2 adrenergic receptors
by inhibiting endothelin receptors
by inhibiting beta-adrenergic receptors


  Last update : June 19, 2005  
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