Serotonin alpha 2 antagonist effects

Mechanism of Action An ergotamine derivative and alpha-adrenergicblocker that directly stimulates vascular smooth muscle, resulting in peripheral and cerebral vasoconstriction. May also have antagonist effects on serotonin. Therapeutic Effect Suppresses vascular headaches. 

Nefazodone [Serzone] Slight inhibition of serotonin and norepinephrine reuptake may also block CNS serotonin receptors Sedating useful in agitation May cause orthostatic hypotension because of antagonistic effect on vascular alpha-1 receptors... 

In contrast, Bach et al (27) reported that the pyrazole derivative (LY 141865) is devoid of alpha and serotonin agonist and antagonist effects. Preliminary studies in our laboratories demonstrated that LY 141865 is a potent DA2 agonist without alpha-adrenergic or DAj activity. 

Alpha-receptor blocking effects can be demonstrated for many Hi antagonists, especially those in the phenothiazine subgroup, eg, promethazine. This action may cause orthostatic hypotension in susceptible individuals. Beta-receptor blockade is not observed. Serotonin-Blocking Action... 

As of yet, the pharmacological actions of Serzone and Desyrel are not completely understood. Like SSRIs they inhibit serotonin uptake. There is also evidence that they antagonize 5-HT2 serotonin receptors. Because of these two functions, Serzone and Desyrel are often referred to as SARIs (serotonin antagonists/reuptake inhibitors). Serzone also inhibits norepinephrine reuptake while Desyrel slightly stimulates alpha-adrenergic receptors. These small differences in pharmacological action can cause widely varying side effects, which will be discussed later on. 

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