Synergistic and persistent interaction between the D2 agonist, bromocriptine, and the D1 selective agonist, CY 208-243.
In mice pretreated with reserpine and alpha-methyl-DL-p-tyrosine (alpha MPT) to deplete central catecholamines, the D2 dopamine receptor-selective agonist, bromocriptine, at a dose of 10 mg/kg produced no locomotor activity. The D1-selective agonist, CY 208-243, generated a dose-dependent locomotor response in this animal model for Parkinson's disease; low doses elicited little or no effect while higher doses resulted in a short burst of locomotor activity (2 h). The combination of CY 208-243 and bromocriptine had a dramatic synergistic effect on locomotion. Most importantly, this combination of D1 and D2 agonists converted a brief (2 h) effect on locomotion to one which persisted for up to 6 h. These results suggest that the combination of D1 and D2 dopamine receptor agonists can affect both the intensity and the persistence of a locomotor response.
Department of Pharmacology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
H A
HA
Robertson
M R
MR
Peterson
G G
GG
Worth
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004357:Drug Synergism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010617:Phenanthridines / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D015259:Dopamine Agents; D007211:Indoles; D008781:Methyltyrosines; D010617:Phenanthridines; D017447:Receptors, Dopamine D1; C054531:CY 208-243; D001971:Bromocriptine; D019805:alpha-Methyltyrosine; D012110:Reserpine