Dopaminergic mechanisms in hemiparkinsonian monkeys.
The motor effects of direct agonists which act selectively on certain dopamine receptors were studied in monkeys rendered hemiparkinsonian by unilateral intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The D-2 dopamine agonist, LY 171555, but not the D-1 agonist, SKF 38393, reduced parkinsonian signs and induced rotation away from the side of the nigral lesion. When administered together, SKF 38393 diminished the LY 171555-induced turning in a dose-dependent manner. A selective D-1 antagonist, SCH 23390, induced mild and brief rotation when administered alone. These results suggest that D-2 receptor stimulation is necessary to ameliorate parkinsonism, but that pharmacologic manipulation of both D-1 and D-2 receptors may be required for an optimal therapeutic response.
Barone
P
P
Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Bankiewicz
K S
KS
Corsini
G U
GU
Kopin
I J
IJ
Chase
T N
TN
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001696:Biomechanical Phenomena; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D019257:Quinpirole; D012399:Rotation
D001552:Benzazepines; D004873:Ergolines; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine