Alpha agonists selective

Beta receptors of the beta-1 subtype mediate an increase in heart rate and increased force of contraction they are also found in the central nervous system. E and NE are equaHy potent agonists and selective antagonists are atenolol [29122-68-7] and betaxolol [63659-18-7]. Beta-2 receptors are weH known for their involvement in relaxing bronchioles. E is a more potent agonist than NE procaterol [72332-33-3] is a selective agonist ICl 118551 and a-methylpropranolol are selective antagonists. A particular amine may act on both alpha and beta receptors or predominandy on one type. NE acts mainly on alpha-1, E on both alpha and beta, and isoprotemol [7683-59-2] almost exclusively on beta receptors. Numerous antagonists also differentiate between... 

Stauffer SR, Coletta CJ, Tedesco R, Nishiguchi G, Carlson K, Sim J, Katzenellenbogen BS, Katzenellenbogen JA (2000) Pyrazole ligands structure-affinity/activity relationships and receptor-alpha-selective agonists. J Med Chem 43 4934-4947... 

BETA-BLOCKERS COCAINE Risk of hypertensive crisis Cocaine produces both alpha- and beta-adrenergic agonist effects selective beta-blockade leads to unopposed alpha-agonism (vasoconstriction) Avoid concurrent use... 

Lopez-Rodriguez ML et al. (1996) Synthesis and structure-activity relationships of a new model of arylpiperazines. 1. 2-[[4-(o-Methoxyphenyl)piperazin-l-yl]methyl]-1, 3-dioxoperhydroimidazo[l,5-alpha]pyridine a selective 5-HTlA receptor agonist. J Med Chem 39(22) 4439-4450... 

Wijayaratne AL, McDonnell DP (2001) The human estrogen receptor-alpha is a ubiq-uitinated protein whose stability is affected differentially by agonists, antagonists, and selective estrogen receptor modulators. J Biol Chem 276 35684-35692... 

Hwa, J., Graham, R.M. and Perez, D.M. (1995) Identification of critical determinants of alpha 1-adrenergic receptor subtype selective agonist binding. The Journal of Biological Chemistry, 270, 23189-23195. 

Nicotinic receptors are of the ionotropic type which, on stimulation by acetylcholine, nicotine or related agonists, open to allow the passage of sodium ions into the neuron. There are structural differences between the peripheral and neuronal receptors, the former being pentamers composed of two alpha and one beta, gamma and delta sub-units while the latter consist of single alpha and beta sub-units. It is now known that there are at least four variants of the alpha and two of the beta sub-units in the brain. In Alzheimer s disease it would appear that there is a selective reduction in the nicotinic receptors which contain the alpha 3 and 4 sub-units (Figure 2.9). 

Mechanism of Action An ocular alpha-adrenergic agent that is a relatively selective alphaj receptor agonist. Therapeutic Effect Reduces intraocular pressure. 

Gastrointestinal tract. Relaxation of GIT smooth muscle can be brought about by both a and (3 stimulant agents. Alpha stimulants especially selective agonists, decrease muscle activity indirectly by presynaptically reducing the release of catecholamines, a -receptors may also decrease salt and water flux into the lumen of the intestine. 

Tizanidine (Zanaflex) is classified as an alpha-2 adrenergic agonist, meaning that this drug binds selectively to the alpha-2 receptors in the CNS and stimulates them. Alpha-2 receptors are found at various locations in the brain and spinal cord, including the presynaptic and postsynaptic membranes of spinal interneurons that control alpha motor neuron excitability. Stimulation of these alpha-2 receptors inhibits the firing of interneurons that relay information to the alpha motor neuron that is, interneurons that comprise polysynaptic reflex arcs within the spinal cord.27 Tizanidine appears to bind to receptors on spinal interneurons, decrease the release of excitatory neurotransmitters from their presynaptic terminals (presynaptic inhibition), and decrease the excitability of the postsynaptic neuron (postsynaptic inhibition).40 Inhibition of spinal interneurons results in decreased excitatory input onto the alpha motor neuron, with a subsequent decrease in spasticity of the skeletal muscle supplied by that neuron. 

Oxymetazoline (Afrin, Visine, many others). This drug is used in nose drops and nasal sprays to decrease nasal congestion through alpha- 1-mediated vasoconstriction. Higher or systemic doses may also cause hypotension, presumably because central nervous system (CNS) alpha-2 receptors are stimulated in a manner similar to clonidine (see Alpha-2-Selective Agonists ). Oxymetazoline can also be administered as eye drops to decrease redness and minor eye irritation. 

Alpha-2-selective drugs are used primarily in the treatment of hypertension and spasticity. When treating hypertension, these drugs stimulate alpha-2 receptors located in the brain and brainstem. When stimulated, these central alpha-2 receptors exert an inhibitory effect on sympathetic discharge from the vasomotor center in the brainstem.34 Diminished sympathetic discharge results in a decrease in blood pressure. The use of alpha-2 agonists in lowering blood pressure is discussed in more detail in Chapter 21. 

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