Antagonists alpha

Alpha antagonists are administered primarily to reduce peripheral vascular tone by blocking the alpha-1 receptors located on vascular smooth muscle. When stimulated by endogenous catecholamines (norepinephrine, epinephrine), the alpha-1 receptor initiates vasoconstriction. 

Consequently, alpha antagonists are used in conditions where peripheral vasodilation would be beneficial. A principal application of these agents, for instance, is in treating hypertension.26 39 These drugs seem to attenuate the peripheral vasoconstriction me- 

Certain alpha-1 blockers such as doxazosin have been used extensively in treating benign prostatic hyperplasia (BPH).23,32 Alpha-1 receptors located on smooth muscle in the prostate capsule, neck of the bladder, and urethra cause muscle constriction that restricts urine flow and the ability to empty the bladder. By blocking these receptors, alpha-1 antagonists relax these smooth muscles and allow men with BPH to void urine more easily and completely.12 32 

A group of drugs known collectively as ergot derivatives display some alpha-blocking ability as well as other unique properties. Ergot alkaloids and ergoloid mesylates and are used clinically for diverse problems, including the treatment of vascular headache and improvement of mental function in pre-senile dementia. 

Because the primary uses of alpha antagonists involve their ability to decrease vascular tone, the clinically useful alpha antagonists tend to be somewhat alpha-1 selective. Alpha-2 receptors should not be selectively antagonized because this event may ultimately lead to an increase in peripheral vascular tone through an increase in sympathetic discharge. Certain alpha-2 receptors are located in the brainstem, and stimulation of these receptors appears to decrease sympathetic outflow from the vasomotor center. Thus, blocking these centrally located alpha-2 receptors is counterproductive when a decrease in vascular tone is desired. 

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Marwaha, J., and Aghajanian, G. K. (1982) Relative potencies of alpha-1 and alpha-2 antagonists... 

Similarly, alpha 2 antagonists do not allow norepinephrine to turn off serotonin release. Therefore, serotonergic neurons become disinhibited (Fig. 7 —7). Similarly to their actions at noradrenergic neurons, alpha 2 antagonists act at serotonergic neurons to cut the brake cable of noradrenergic inhibition norepinephrine brake on serotonin shown in Figs. 5—47 and 5—48. Serotonin release is therefore increased (Fig. 7-7). 

A second mechanism to increase serotonin release after administration of an alpha 2 antagonist may be even more important. Recall that norepinephrine neurons from the locus coeruleus innervate the cell bodies of serotonergic neurons in the midbrain raphe (Figs. 5-47 and 5—48). This noradrenergic input enhances serotonin release... 

Two other alpha 2 antagonists are marketed as antidepressants in some countries (but not the United States), namely, mianserin (worldwide except in the United... 

In this chapter, we have discussed the mechanisms of action of several of the newer classes of antidepressant drugs and mood stabilizers. The acute pharmacological actions of these agents on neurotransmitter receptors have been described. The reader should now understand the proposed mechanisms of action of dual reuptake inhibitors, alpha 2 antagonists, and serotonin 2A antagonists/serotonin reuptake inhibitors, as well as those of lithium and the anticonvulsant mood stabilizers for the treatment of bipolar disorder, particularly the acute manic phase. 

Norepinephrine One theory about the biological basis of panic disorder is that there is an initial excess of norepinephrine (Fig. 9—3). This theory is supported by evidence that panic disorder patients are hypersensitive to alpha-2 antagonists and hyposensitive to alpha-2 agonists. Thus, yohimbine, an alpha-2 antagonist, acts as a promoter of norepinephrine release by cutting the brake cable of the presyn-aptic norepinephrine autoreceptor, as shown earlier in Figure 7—6. The consequence... 

Rascol O, Sieradzan K, Peyro-Saint-Paul H, Thalamas C, Brefel-Courbon C, Senard JM, Ladure P, Montastruc JL, Lees A (1998) Efaroxan, an alpha-2 antagonist, in the treatment of progressive supranuclear palsy. Mov. Disord. 13 673-676. 

Alpha 2 antagonist NaSSA (noradrenaline and specitic serotonergic agent) dual serotonin and norepinephrine agent antidepressant... 

The exact mechanism of action of tizanidine is unknown. It acts in the CNS at different sites, both at spinal and supraspinal level, which accoimts for its anti-spastic effect. Its main affect is via its alpha-2 ago-nism though its affect on imidazoline receptors may also play a role, as shown by reversal of its anti-spastic effects by alpha-2 antagonists such as yohimbine and idazoxan in animals [1,2]. 

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