Alpha-adrenergic receptors pharmacology

Kunisawa et al. (1985) performed a pharmacological study of alpha adrenergic receptor subtypes in smooth muscle of human urinary bladder base and prostatic urethra. 

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. 

I. Pharmacology. Norepinephrine is an endogenous catecholamine that stimulates mainly alpha-adrenergic receptors. It is used primarily as a vasopressor to increase systemic vascular resistance and venous return to the heart. Norepinephrine is also a weak beta-1-adrenergic receptor agonist, and it may increase heart rate and cardiac contractility in patients with shock. Norepinephrine is not effective orally and is erratically absoihed after subcutaneous injection. After intravenous administration, the onset of action is nearly immediate, and the duration of effect is 1-2 minutes after the infusion is discontinued. 

I. Pharmacology. Phentolamine is a competitive presynaptic and postsynaptic alpha-adrenergic receptor blocker that produces peripheral vasodilation. By acting on both venous and arterial vessels, it decreases total peripheral resistance and venous return. It may also stimulate beta-adrenergic receptors, causing cardiac stimulation. Phentolamine has a rapid onset of action (usually 2 minutes) and short duration of effect (approximately 15-20 minutes). 

Rossier, O., Abuin, L., Fanelli, F., Leonardi, A. and Cotecchia, S. (1999) Inverse agonism and neutral antagonism at alpha(la)- and alpha(lb)-adrenergic receptor subtypes. Molecular Pharmacology, 56, 858-866. 

Pharmacology The proposed mechanism of action of methyidopa is probably due to the drug s metabolism to alpha-methyl norepinephrine, which lowers arterial pressure by the stimulation of central inhibitory -adrenergic receptors, false neurotransmission or reduction of plasma renin activity. 

Pharmacology Initially, clonidine stimulates peripheral -adrenergic receptors producing transient vasoconstriction. Stimulation of alpha-adrenergic in the brain stem results in reduced sympathetic outflow from the CNS and a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Pharmacokinetics Blood pressure declines within 30 to 60 minutes after an oral... 

Pharmacology Brimonidine is an alpha-2 adrenergic receptor agonist. It has a peak ocular hypotensive effect occurring at 2 hours postdose. Brimonidine has a dual mechanism of action it reduces aqueous humor production and increases uveoscleral outflow. 

Still other pharmacologic actions are associated with the conventional antipsychotic drugs. These include generally undesired activity at alpha 1 adrenergic receptors as well as at histamine 1 receptors, as already discussed (Fig. 11—7). Thus, conventional antipsychotic drugs have activities at three of the same neurotransmitter receptors... 

In summary, adrenergic receptors can be subclassified according to their location and affinity for specific pharmacologic agents. Table 18-2 summarizes the receptor subtypes that are located on the primary organs and tissues in the body, and the associated response when the receptor is stimulated. Exactly which receptor subtype is located on any given tissue depends on the tissue in question. Note that some tissues may have two or more different subtypes of adrenergic receptor (e.g., skeletal muscle arterioles appear to have alpha-1 and beta-2 receptors). Also, the response of a tissue when the receptor is stimulated is dependent on the specific receptor-cell interaction. Stimulation of the vascular alpha-1 receptor, for instance, results in smooth-muscle contraction and vasoconstriction, whereas stimulation of the intestinal alpha-1 receptor results in relaxation and decreased intestinal motility. This difference is caused by the way the receptor is coupled to the cell s internal biochemistry at each location. As discussed in Chapter 4, the surface receptor at one cell may be coupled to the... 

Porter JE, Perez DM. Characteristics for a salt-bridge switch mutation of the alpha(lb) adrenergic receptor. Altered pharmacology and rescue of constitutive activity. J Biol Chem 1999 274 34,535-34,538. 

Forray C, Bard JA, Wetzel JM, et al. The a,-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha lc subtype. Mol Pharmacol 1994 45 703-708. 

Levodopa shonld be nsed with cantion in patients with varions cardiovascnlar disorders. The peripheral decarboxylation of levodopa markedly increases the concentration of dopamine in the blood. Dopamine is a pharmacologically active catecholamine that inflnences alpha- and beta-adrenergic receptors. 

Buerkle H, Yaksh TL. Pharmacological evidence for different alpha 2-adrenergic receptor sites mediating analgesia and sedation in the rat. BrJ Anaesth 1998 81(2) 208-215. 

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