A-412997 is a selective dopamine D4 receptor agonist in rats
| Autor: | Robert B. Moreland, Jorge D. Brioni, Kennan C. Marsh, Gin C. Hsieh, Jill M. Wetter, Meena V. Patel |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Agonist medicine.medical_specialty Pyridines medicine.drug_class Clinical Biochemistry Pharmacology Biology Toxicology Biochemistry Cell Line Behavioral Neuroscience Dopamine receptor D1 Dopamine receptor D2 Internal medicine Acetamides Dopamine receptor D5 medicine Animals Humans Rats Wistar Biological Psychiatry Penile Erection Receptors Dopamine D4 Rats Apomorphine Endocrinology Dopamine receptor A-412997 Dopamine Agonists Endogenous agonist medicine.drug |
| Zdroj: | Pharmacology Biochemistry and Behavior. 82:140-147 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2005.08.001 |
| Popis: | A-412997 (2-(3',4',5',6'-tetrahydro-2'H-[2,4'] bipyridinyl-1'-yl)-N-m-tolyl-acetamide) is a highly selective dopamine D4 receptor agonist that binds with high affinity to rat dopamine D4 and human dopamine D4.4 receptors (Ki=12.1 and 7.9 nM, respectively). In contrast to the dopamine D4 receptor agonists PD168077 and CP226269, A-412997 showed a better selectivity profile and no affinity1000 nM for other dopamine receptors or any other proteins in a panel of seventy different receptors and channels. In functional assays using calcium flux, A-412997 was a potent full agonist at rat dopamine D4 receptors (28.4 nM, intrinsic activity=0.83) and did not activate rat dopamine D2L receptors, unlike CP226269. Dopamine D4 receptor selective agonists have been shown to induce penile erection in rats by central mechanisms. A-412997 induces penile erection in a conscious rat model (effective dose=0.1 micromol/kg, s.c.) with comparable efficacy as the nonselective D2-like agonist, apomorphine. When dosed systemically, A-412997 crossed the blood brain barrier rapidly and achieved significantly higher levels than PD168077. A-412997 is a highly selective dopamine D4 receptor agonist and a useful tool to understand the role of dopamine D4 receptors in rat models of central nervous system processes and disease. |
| Databáze: | OpenAIRE |
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