Receptors beta-adrenergic

Olanzapine High — serotonin 5-HT2a. 5-HT20 dopamine D-, D2, D3, D4, muscarinic M-, M2, M3, M4, M5, histamine H-, alpha- -adrenergic Weak— GABAa, benzodiazepine receptor, beta-adrenergic... 

Alpha-adrenergic antagonists are used primarily as antihypertensive drugs because of their ability to block vascular alpha-1 receptors. Beta-adrenergic antagonists (beta blockers) are administered primarily for their inhibitory effects on myocardial function and are used in the prevention and treatment of hypertension, angina pectoris, arrhythmias, and myocardial reinfarction. Many of the drugs introduced in this chapter are discussed further in chapters that deal with the specific clinical conditions (e.g., hypertension, asthma, and other disorders). 

Class II antiarrhythmic drugs include beta (( -adrenergic blocking drugs, such as acebutolol (Sectral), esmolol (Brevibloc), and propranolol (Inderal). These drugp also decrease myocardial response to epinephrine and norepinephrine (adrenergic neurohormones) because of their ability to block stimulation of p receptors of the... 

Hugget D, Brook B, Peterson B, Foran CM, Schlenk D (2002) Toxicity of selected beta adrenergic receptor-blocking pharmaceuticals (B-blockers) on aquatic organisms. Arch Environ Contam Toxicol 43 229-235... 

Thus three lines of evidence define the rapidly dissociating receptor as the LR complex. Conditions known to uncouple R from G--first, guanine nucleotide and second, pertussis toxin—produce LR third, reconstitution of G protein restores receptor affinity, sensitivity to guanine nucleotide, and effector activation. In this sense, the ligand and binding behavior of this system is analogous to that of the beta-adrenergic receptor, where the LR and LRG complexes have already been studied with purified proteins and reconstituted membrane preparations (2,i0). 

Hnggett, D.B., Brooks, B.W., and Peterson, B. et al. (2002). Toxicity of select beta adrenergic receptor blocking pharmaceuticals (beta blockers) on aqnatic organisms. Archives Environmental Contamination and Toxicology 41, 229-235. 

The Beta-Adrenergic Receptors, edited by John P. Perkins,... 

Howard MJ, Hughes RJ, Motulsky HJ, Mullen MD, Insel PA. Interactions of amiloride with alpha- and beta-adrenergic receptors amiloride reveals an allosteric site on alpha 2-adrenergic receptors. Mol Pharmacol 1987 32 53-58. 

Hausdorff, W. P., Caron, M. G. Lefkowitz, R. J. (1990). Turning off the signal desensitization of beta-adrenergic receptor function. EASES J. 4, 2881-9. 

Beta-2-adrenergic receptor Beta-2-adrenergic receptor Beta-2-adrenergic receptor polymorphisms affect Susceptibility to lower airway reactivity... 

Beta-1, beta-2, and beta-3 adrenergic receptors are G-protein-coupled receptors. Beta-1 and beta-2 receptors mediate the positive inotropic, chronotropic, and dro-motropic effects of the endogenous catecholamines epinephrine and norepinephrine. The beta-3 subtype seems to play a role in regulating thermogenesis and lipid mobilization in brown and white adipose tissue. Several coding and promoter polymorphisms of these receptors have been identified. Clinical studies in asthma... 

Polymorphisms of the beta adrenergic receptors have also been studied in patients with heart failure and cardiomyopathy, or other complex and rather ill-defined phenotypes. In patients with heart failure due to ischemic or idiopathic dilated cardiomyopathy, the Thrl64Ile polymorphism in the />2-adrerioreceplor was significantly associated with survival rate at one year [62]. Similarly, the Ser49Gly polymorphism of the /Vadrenoreceptor gene has been linked to the improved survival of patients with idiopathic cardiomyopathy [63]. However, sample size was limited in those studies and results need to be confirmed in adequately powered studies. 

Strader C, Sigal I, Register R, Cande-lore M, Rands E, Dixon R. Identification of residues required for ligand binding to the beta-adrenergic receptor. Proc Natl Acad Sci USA 1987 84 4384-4388. 

Lefkowitz, R. J., Haber, E., and O Hara, D. (1972). Identification of the cardiac beta-adrenergic receptor protein Solubilization and purification by affinity chromatography. Proc. Natl. Acad. Sci. USA 69, 2828-2832. 

Fecho, K., Dykstra, L. A., andLysle, D. T., Evidence for beta adrenergic receptor involvement in the immunomodulatory effects of morphine, J. Pharmacol. Exp. Ther., 265,1079, 1993. 

Limbird, L. E., Meyts, P. D., and Lefkowitz, R. J. (1975) Beta-adrenergic receptors evidence for negative cooperativity. Biochem. Biophys. Res. Commun. 64,1160-1168. 

One of the few examples of decreased susceptibility among elderly is the effect of catecholamines on the heart. There is a down-regulation of beta-adrenergic receptors and a reduced response to beta-adrenergic stimulation (Turnheim 1998). This results in decreased effect of betablockers on heart rate and stroke volume. In the elderly betablockers may be less effective than other drugs against hypertension and they should not be considered appropriate for first-line therapy of uncomplicated hypertension in the elderly (Grossman and Messerli 2002). 

Clinical Trials. In Phase I studies, good documentation and additional investigations should be standard practice. Serious reactions are pretty unusual in these studies, which will detect only very common ADRs, in particular those that are pharmacologically mediated (e.g., bradycardia with beta adrenergic receptor antagonists). 

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

Huggett, D.B., Khan, I.A., Foran, C.M., and Schlenk, D., Determination of beta-adrenergic receptor blocking pharmaceuticals in United States wastewater effluent, Environ. Pollut., 121, 199-205, 2003. 

Atenolol stimulation of arteriolar contraction Beta-adrenergic receptor anatagonist, reduces cardiac output... 

CNS inflammation induced by IPS downregulates 1A1 activity in rat loss prevented by beta adrenergic receptor agonist (Abdulla and Renton, 2005). 

Abdulla D, Renton KW. 2005. Beta-adrenergic receptor modulation of the LPS-mediated depression in CYPIA activity in astrocytes. Biochem Pharmacol 69 741-750. 

---