A-agonists

Workers at Lilly prepared the oxazole-containing partial ergot alkaloid, 27, a 5-HTl A agonist, through van Leusen reaction of aldehyde 26. ... 

Current evidence suggests that PPAR activation may limit inflammation and hence atherosclerosis. Both PPAR-a and PPAR-y can reduce T-cell activation, as shown by decreased production of EFN-y. PPAR-a agonists also rqness endothelial VCAM-1 expression and inhibit the inflammatory activation of vascular SMCs, while PPAR-y agonists repress endothelial chemokine expression and decrease macrophage MMP production. 

A series of 2-(4-chlorophenoxy)-3-oxoalkanoate were reduced by baker s yeast, and Kluyveromyces marxianus. Yeast reduction of ethyl 2-(4-chlorophenoxy)-3-oxo-3-phenylpropanoate (R=Ph) afforded enantiomerically pure ethyl 2R, 3S)-2-(4-chlorophenoxy)-3-hydroxy-3-phenylpropanoate out of the four possible stereoisomers in >99% de [29h]. Although baker s yeast reduction of butanoate (R = CFl3) was not selective (92% de), the use of K. marxianus afforded (2R, 3S)-isomer selectively [29i]. The products are intermediates for potential peroxisome prolifera-tor-activated receptor isoform a-agonists (Figure 8.39a). 

Phenylephrine is a fast-acting, short-duration a, agonist. Phenylephrine has primarily vascular effects, and does not impair cardiac or renal function. Phenylephrine is useful when tachycardia limits the use of other vasopressors.24,27-28... 

Discontinue antihypertensive medications IV fluids to maintain systolic blood pressure greater than 80-90 mm Hg or vasopressor support with an a-agonist such as phenylephrine as indicated. 

Treat bronchospasm with a -agonist given intermittently or continuously, consider the use of aminophylline 5.6 mg/kg as an IV loading dose, given over 20 minutes, or to maintain a blood level of 8— 15 mcg/mL... 

Lancel, M. and Langebartels, A. (2000) gamma-aminobutyric Acid(A) (GABA(A)) agonist 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol persistently increases sleep maintenance and intensity during chronic administration to rats../. Pharmacol. Exp. Ther. 293,1084-1090. 

Signal transduction at G-protein-cou-pled receptors uses essentially the same basic mechanisms (A). Agonist binding to the receptor leads to a change in receptor protein conformatioa This change propagates to the G-protein the a-subunit exchanges GDP for GTP, then dissociates from the two other subunits, associates with an effector protein, and alters its functional state. The a-subunit slowly hydrolyzes bound GTP to GDP. 

Blier P, Ward NM (2003) Is there a role for 5-HT (1 A) agonists in the treatment of depression Biol Psychiatry 53 193-203... 

There are differences between the receptors on nerves (presynaptic receptors) and those on effector cells (postsynaptic receptors). Furthermore, some a-agonists and antagonists exhibit selectivity for one of these receptor types. Terminology classifies receptors as either i or tt2. i-Receptors are those whose stimulation has traditionally been associated with the postsynaptic a-receptors of smooth muscle, while a2-receptors are those originally associated with the presynaptic a-re-ceptors of peripheral nerves. However, the designation of receptors as either or 2 cannot be categorized strictly by anatomical location (i.e., presynaptic or postsynaptic), since evidence now indicates that az-recep-tors occupy, in addition to peripheral nerves, a variety of sites including smooth muscle, adrenal medullary cells, the brain, and melanocytes. 

Absolute selectivity of action for i- or a2-receptors does not exist for any available a-agonists and antagonists. Furthermore, as is the case with (3-receptors, a given effector tissue may contain more than one a-receptor subtype. Recent evidence suggests that in addition to ai-receptors, vascular smooth muscle may possess a2-receptors. Although the functional importance of a2-re-ceptors in blood vessels seems to be less than that of aj-receptors, this can account for certain clinical observations, as for example the pressor response that occurs upon initiation of treatment with the az-agonist clonidine. 

Phenylephrine hydrochloride (Neo-Synephrine) is a pure a-agonist that is occasionally used for subarachnoid block and is marketed with procaine for use in dentistry. It has little direct cardiac effect. 

Pyrantel pamoate (Antiminth) is a agonist at the nicotinic acetylcholine receptor, and its actions result in depolarization and spastic paralysis of the helminth muscle. Its selective toxicity occurs primarily because the neuromuscular junction of helminth muscle is more sensitive to the drug than is mammalian muscle. This drug is administered orally, and because very little is absorbed, high levels are achieved in the intestinal tract. Less than 15% of the drug and its metabolites are excreted in urine. 

Antihypertensives typically used in child psychiatry include a agonists (clonidine, guanfacine) and beta-blockers (propranolol, nadolol). 

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