Interaction of Dexanabinol (HU-211), a novel NMDA receptor antagonist, with the dopaminergic system
| Autor: | Yafit Berkovitch, Anat Biegon, Avi Bar-Joseph, Sarina Striem |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class Biology Pharmacology Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley Mice Dopamine receptor D1 Dopamine Internal medicine Cyclic AMP medicine Animals Dronabinol Cells Cultured Cerebral Cortex Neurons Catalepsy Mice Inbred BALB C Receptors Dopamine D1 Dopaminergic Rats Endocrinology Dopamine receptor Competitive antagonist Dopamine Antagonists NMDA receptor Dizocilpine Maleate Excitatory Amino Acid Antagonists Endogenous agonist medicine.drug |
| Zdroj: | European Journal of Pharmacology. 338:205-213 |
| ISSN: | 0014-2999 |
| Popis: | The interaction of 7-hydroxy-delta6-tetrahydrocannabinol 1,1-dimethylheptyl (Dexanabinol: HU-211), a novel NMDA receptor antagonist, with the dopaminergic system was examined using in vitro and in vivo systems. HU-211 (50 or 100 microM) inhibited the binding of [3H]R(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepi n-7-ol hydrochloride ([3H]SCH-23390), a dopamine D1 receptor antagonist, by 29.7 +/- 1.8% and 52.7 +/- 6.3%, respectively. HU-211 10 microM, like the dopamine D1 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF-38393), enhanced the conversion of [3H]adenine to cyclic AMP (cAMP) (51.8 +/- 29.7% and 35.6 +/- 21.5% over control, respectively). The HU-211-induced increase was not inhibited by SCH-23390. HU-211 together with the dopamine D1 receptor agonist caused a synergistic elevation (314.7 +/- 14.3%). HU-211 reduced the catalepsy induced by dopamine receptor antagonists. At 10 mg/kg, HU-211 significantly (P < 0.001) reduced the catalepsy time induced by D1, D2 and non-selective dopamine receptor antagonists. Overall, the results of the present study demonstrate that HU-211 interacts with the dopaminergic system and enhances activity at the dopamine D1 receptor level. This activity may have implications in diseases involving the dopaminergic system, such as Parkinson's disease. |
| Databáze: | OpenAIRE |
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