Behavioral characterization of the new potent nonselective dopamine agonist pergolide.
Pergolide (LY127809, CAS 66104-23-2), a non-selective dopamine agonist, was evaluated for broad behavioral properties in a wide range of pharmacological tests. The selective dopamine2(D2) agonist, bromocriptine, served as a reference standard for those tests where behavioral activity was noted with pergolide. Pergolide and bromocriptine were administered orally to mice at doses of 0.3-30 and 3-300 mg/kg, respectively. Both compounds produced biphasic effects on spontaneous activity, increased hexobarbital-induced sleep time, and lowered mouse body temperature. Qualitative changes with pergolide were observed with some mice showing hyporeactiveness, ptosis, slowed respiration and placing loss. Reserpine-induced hypothermia was reversed by pergolide with significant increases in the body temperature of reserpine-treated mice. However, a further reduction in the body temperature of reserpinized hypothermic mice was seen following bromocriptine administration. Acetic acid-induced writhing and performance on the rotarod were both impaired by higher doses of pergolide. Bromocriptine administration also reduced writhing at higher doses but did not alter performance on the rotarod. Pergolide had no effect on seizure activity as evaluated by electroshock, pentylenetetrazol (pentetrazol) or strychnine. Oxotremorine-induced tremors and salivation, grip strength, and tail-flick were not affected by pergolide. Neither pergolide nor bromocriptine altered established shuttle-avoidance behavior in rats at oral doses of 0.1 to 30 mg/kg. Behavioral assessment of pergolide in dogs was complicated by severe emetic responses at clinically relevant doses greater than 0.003 mg/kg. In summary, these data suggest that pergolide produces a behavioral profile which is characteristic of dopaminergics.(ABSTRACT TRUNCATED AT 250 WORDS)
Helton
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Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana.
Modlin
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Williams
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PD
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects; D010095:Oxotremorine; D010479:Pergolide / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012472:Salivation / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D000700:Analgesics; D010479:Pergolide; D001971:Bromocriptine; D010095:Oxotremorine; D012110:Reserpine