The most frequent side effects when using /¡-adrenoblockers are feelings of fatigue, coldness in the extremities, and also an increase in the level of triglycerides and lipoproteins in the blood.


The stimulation of a-adrenergic receptors in specific regions of the CNS leads to hypotension.

The mechanism of action of these drugs is caused by stimulation of a^adrenoreceptors in the inhibitory structure of the brain. It is believed that interaction of these drugs with a2-adrenergic receptors is expressed in the suppression of vasomotor center neurons of the medulla, and reduction of hypothalamus activity, which leads to a decline in sympathetic impulses to the vessels and the heart. In summary, cardiac output and heart rate are moderately reduced, and consequently arterial pressure is reduced.

The clinically beneficial antihypertensive drugs of this series such as clonidine, guan-abenz, and guanfacin evidently act identically by affecting a^adrenergic receptors. Methyldopa, examined together with the aforementioned drugs, is transformed in the body into a-methylnoradrenaline, which, by stimulating a^adrenergic receptors, inhibits sympathetic impulses, thus lowering arterial pressure.

Clonidine (11.1.34): The synthesis is described in Chapter 11.

Clonidine is a selective a2-adrenergic agonist that exhibits pronounced hypotensive action that is associated with a reduction of overall peripheral vascular resistance, decline in frequency of cardiac contraction, and reduced cardiac output. Clonidine is the drug of choice for treating various degrees of hypertension when used in combination with oral diuretics.

Clonidine is used in various forms of hypertonic diseases and for relieving hypertonic crises. It is also used in ophthalmological practice for treating wide-angle glaucoma. Synonyms of clonidine are gemiton, catapresan, and clofeline.

Guanabenz: Guanabenz, [(2,6-dichlorobenzyliden) amino] guanidine (22.3.1), is synthesized in one step by reacting 2,6-dichlorobenzaldehyde with amino guanidine [1-3].

Cl Cl

NH NH <i V-CHO + H2N-NH-C-NH2 -\_/~ CH=NH—NH-C-NH2

Cl Cl

Guanabenz is an a2-adrenergic agonist that exhibits pronounced hypotensive action, and that is associated with a reduction of overall peripheral vascular resistance, decline in frequency of cardiac contractions, and reduced cardiac output.

It is used both independently and in combination with oral diuretics for treating various degrees of hypertension. A synonym of this drug is vitensin.

Guanfacin: Guanfacin, N-amidino-2-(2,6-dichlorophenyl)acetamide (22.3.2), is also synthesized in a very easy synthesis of reacting the acid chloride or ester of 2,6-dichlorophenylacetic acid with guanidine [4-7].

Cl Cl


Guanidine operates exactly by the same mechanism as clonidine and guanabenz, and it is used for the same indications. A synonym of this drug is estulic.

Methyldopa: Methyldopa, (-)-3-(3,4-dihydroxyphenyl)-2-methylalanine (22.2.5), is synthesized by a few methods that are only slightly different. The first method is from 3,4-dimethoxyphenylacetone, which undergoes a Strecker-Zelinski reaction using potassium cyanide and ammonium carbonate, to give 4-methyl-4-(3,4-dimethoxybenzyl-hydantoine (22.3.3), which is further hydrolyzed in the presence of barium hydroxide to give (±)-3-(3,4-dimethoxyphenyl)-2-methylalanine (22.3.4). This undergoes acetylation at the amino group, and the racemic mixture is then separated using (-)-l-phenylethylamine. The isolated isomer is hydrolyzed using hydrobromic acid, which simultaneously removes the methoxy- and acetyl groups to give the desired (-)-3-(3,4-dihydroxyphenyl)-2-methylalanine (22.3.5) [8-10]. Alternative syntheses have been proposed [11-13].


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