I agonist

IV. MIXED [i AGONIST/5 ANTAGONISTS A. Prototypes and Structure-Activity Relationships... 

Muller, C. E. Adenosine receptor ligands - recent developments part I. agonists, Curr. Med. Chem. 2000, 7, 1269-1288. 

As described in section 2.3, metabotropic receptors are divided into families, based upon second messenger mechanisms and functional effect. Group I receptors potentiate presynaptic glutamate release and NMDA receptor-mediated neurotransmission. Therapeutic effectiveness of group I agonists is therefore... 

Despite encouraging preclinical results with Group I agonists, clinical data remain lacking. Further, group I receptors have a markedly different cellular distribution in primates than rodents (Muly et al., 2003 Paquet and Smith, 2003). Primate studies and eventual clinical trials therefore will be needed to validate this target for the treatment of neuropsychiatric disorders. Nevertheless, the preclinical efficacy of these compounds remains encouraging for eventual therapeutic utility. 

D ihydroxyphenyl- Euphorbia helioscopia mGlu-R (Class I) agonist - la... 

P-dV-Methylamino-I,- Cycas circinalis (Cycadaceae) causes mClu-R Class I agonist - 1 a... 

Table 3 Phosphatidylinositol assay from in vitro testing. Experimental agents causing an increase in intracellular free inositol phosphate accumulation are considered to be Group I agonists. Agents inhibiting inositol phosphate accumulation induced by ACPDa are considered to be Group I antagonists...

Entry Group I Agonist ECS (M) Group I Antagonist ec50 (M)... 

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

The distribution plots shown in Figure 5.11 confirm that they can be expected to behave as rather good MT i agonists with weak MT2 partial agonist or antagonist activity. 

Leeb-Lundberg LM, Cotecchia S, DeBlasi A, Caron MG, Lefkowitz RJ. Regulation of adrenergic receptor function by phosphorylation. I. Agonist-promoted desensitization and phosphorylation of a -adrenergic receptors coupled to inositol phospholipid metabolism in DDT1MF-2 smooth muscle cells. J Biol Chem 1987 262 3098-3105. 

Trade names Byetta (Lilly) Exendin Medisorb Exendin Indications Type II Diabetes Mellitus Category Glucagon-like peptide I agonist Incretin mimetic Insulin secretagogue Half-life 2.4 hours... 

Incorporation of o-Arg in position 2 of dermorphin and tetrapeptide analogs yields peptides that are potent opioids in antinociceptive assays in mice (879,882). The tetrapeptide derivative Tyr-D-Arg-Phe-Sar (TAPS)is a potent opioid in antinociceptive assays and causes respiratory stimulation, rather than respiratory depression, that is antagonized by naloxonazine (883) TAPS also antagonizes the respiratory depression caused by dermorphin. On the basis of these results TAPS has been postulated to be a p-i agonist and a antagonist in vivo (883). In contrast, incorporation of L-Tic in position 2 of dermorphin converts the peptide to a 6-receptor antagonist (884). 

Kaczor A, Matosiuk D (2002) Non-peptide opioid receptor ligands - recent advances. Part I. Agonists. Curr Med Chem 9 1567-1589... 

One example of the relevance of this in pharmaceutical chemistry are the two isomers 2-fluoro (2-F-NE) and 6-fluoronorepinephrine (6-F-NE) [21]. The modes of binding of these two different fluorinated isomers to their receptor are, unexpectedly, fundamentally different - 6-F-NE has agonistic a-adrenergic activity whereas 2-F-NE acts as a /i-agonist. This can be explained by the stabilization of two different preferred conformations by internal hydrogen bridges between the aliphatic hydroxy group and the aromatic fluorine (Scheme 4.15). 

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