S. Striem et al., INTERACTION OF DEXANABINOL (HU-211), A NOVEL NMDA RECEPTOR ANTAGONIST, WITH THE DOPAMINERGIC SYSTEM, European journal of pharmacology, 338(3), 1997, pp. 205-213
The interaction of 7-hydroxy-Delta(6)-tetrahydrocannabinol 1,1-dimethy
lheptyl (Dexanabinol; HU-211), a novel NMDA receptor antagonist, with
the dopaminergic system was examined using in vitro and in vivo system
s. HU-211 (50 or 100 mu M) inhibited the binding of -tetrahydro-3-meth
yl-5-phenyl-1H-3-benzazepin-7-ol hydrochloride ([H-3] SCH-23390), a do
pamine D-1 receptor antagonist, by 29.7 +/- 1.8% and 52.7 +/- 6.3%, re
spectively. HU-211 10 mu M, like the dopamine D-1 receptor agonist nyl
-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF-383
93), enhanced the conversion of [H-3]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 D-1 receptor agonist caused a synergistic elevation (314
.7 +/- 14.3%). HU-211 reduced the catalepsy induced by dopamine recept
or antagonists. At 10 mg/kg, HU-211 significantly (P < 0.001) reduced
the catalepsy time induced by D-1, D-2 and non-selective dopamine rece
ptor antagonists. Overall, the results of the present study demonstrat
e that HU-211 interacts with the dopaminergic system and enhances acti
vity at the dopamine D-1 receptor level. This activity may have implic
ations in diseases involving the dopaminergic system, such as Parkinso
n's disease. (C) 1997 Elsevier Science B.V.