Alpha-2 receptor agonist

Zhao, D. and Ren, L.M. (2003) Electrophysiological responses to imidazoline/alpha(2)-receptor agonists in rabbit sinoatrial node pacemaker cells. ActaPharmacolo caSinica,U, 1217-1223. 

Its duration of action is 60-120 minutes, depending on the vascularity of the site blocked as well as added adjuvants such as epinephrine. The drug is 70% protein-bound, with 30% in the free unbound form. It is this 30% that is rapidly cleared by the systemic circulation for hepatic metabolism. The vasoconstrictive properties of epinephrine help to decrease this systemic uptake of the drug and thus to prolong its duration of action. Other adjuvants such as the alpha-2 receptor agonists clonidine and dexmedetomidine have been studied recently and found to prolong the duration of action of lidocaine. Their mechanism of action (specific receptor vs. pharmacokinetic/phar-macodynamic interaction with local anesthetics) and site (central vs. peripheral) of action have not been fully elucidated [6-8]. 

As an alpha-2 agonist, tizanidine decreases presynaptic excitatory neurotransmitter release and postsyn-aptic neurotransmitter effectiveness. Alpha-2 receptor agonists attenuate monosynaptic and polysynaptic reflexes in the spinal cord [25]. Tizanidine decreases excitatory neurotransmitter release and Substance P release from small sensory afferents [28]. Tizanidine decreases locus coeruleus activity, thereby modulating descending motor regulatory pathways [28]. Tizanidine decreases activity of both alpha and gamma motor neurons [28]. 

Russo, R., LoVerme, J., La Rana, G., D Agostino, G., Sasso, O., Calignano, A., and Piomelli, D. (2007). Synergistic antinociception by the cannabinoid receptor agonist anandamide and the PPAR-alpha receptor agonist GW7647. Eur. J. Pharmacol. 566, 117—119. 

Indications Sedation for intensive care unit intubation Category Adrenergic alpha-receptor agonist Half-life 2 hours... 

Trade names Cardiosteril Dopamin Dopamin AWD Dopastat Dynatra Intropin Revimine Indications Hemodynamic imbalances present in shock Category Adrenergic alpha-receptor agonist Catecholamine Inotropic sympathomimetic Half-life 2 minutes... 

Trade names Ectasule Efedron Ephedsol Marax Pretz-D Rynatuss (MedPointe) Vicks Vatronol (Procter Gamble) Indications Nasal congestion, acute hypotensive states, asthma Category Adrenergic alpha-receptor agonist Sympathomimetic Half-life 3-6 hours... 

Category Adrenergic alpha-receptor agonist Antidepressant, tetracyclic... 

Indications Nasal congestion, glaucoma, hypotension Category Adrenergic alpha-receptor agonist Sympathomimetic Half-life 2.5 hours... 

Explain the interaction between MAOIs and alpha-receptor agonists. 

Administration of a MAOI for therapy of depression results in elevated levels of circulating norepinephrine and epinephrine. Concurrent administration of an alpha-receptor agonist results in elevated vascular tension. 

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... 

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... 

Hwa, J. and Perez, D.M. (1996) The unique nature of the serine interactions for alpha 1-adrenergic receptor agonist binding and activation. The Journal of Biological Chemistry, 271, 6322-6327. 

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. 

M. Takasuka, M. Kishi, M. Yamakawa, FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2.alpha., prostacyclin receptor agonist (carbacyclin) and their related compounds in dilute carbon tetrachloride solution Structure-activity relationships, J. Med. Chem. 37 (1994) 47. 

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

Mechanism of Action An alpha-adrenergic agonist that stimulates alphaj-adrenergic receptors. Inhibits sympatheticcardioaccelerat or and vasoconstrictor center to heart, kidneys, peripheral vasculature. Therapeutic Effect Decreases systolic, diastolic blood pressure (BP). Chronic use decreases peripheral vascular resistance. Pharmacohinetics Well absorbed from gastrointestinal (GI) tract. Widely distributed. Protein binding 90%. Metabolized in liver. Excreted in urine and feces. Not removed by hemodialysis. Half-life 6 hr. 

Mechanism of Action An alpha-adrenergic receptor agonist that causes vasoconstriction, reflex bradycardia, inhibits GI smooth muscle and vascular smooth muscle supplying skeletal muscle and increases heart rate and force of heart muscle contraction. Therapeutic Effect Increases both systolic and diastolic pressure. 

Mechanism of Action A vasopressor that forms the active metabolite desglymido-drine, an alphaj-agonist, activating alpha receptors of the arteriolar and venous vasculature. Therapeutic Effect Increases vascular tone and BP. 

Mecfianism of Action Phenylephrine HCl is an alpha-receptor sympathetic agonist used in local ocular disorders because of its vasoconstrictor and mydriatic action. It exhibits rapid and moderately prolonged action, and it produces little rebound vasodilatation. Systemic side effects are uncommon. Therapeutic Effect Vasoconstriction and pupil dilation. 

Alpha receptors are widely expressed in vascular beds, and their activation leads to arterial and venoconstriction. Their direct effect on cardiac function is of relatively less importance. A relatively pure agonist such as phenylephrine increases peripheral arterial resistance and decreases venous capacitance. The enhanced arterial resistance usually leads to a dose-dependent rise in blood pressure (Figure 9-... 

FIGURE 12-6. Postsynaptic alpha 2 adrenergic receptors are postulated to mediate cognitive effects of norepinephrine in the frontal cortex. Direct-acting alpha 2 agonists such as clonidine and guanfacine can be helpful in attention deficit disorder, perhaps because of actions at this site. 

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