The behavioural effects of pramipexole, a novel dopamine receptor agonist.
Pramipexole (SND 919; 2-amino-4,5,6,7-tetrahydro-6-propyl-amino-benzthiazole-dihydroc hlo ride) is a novel dopamine D2 family receptor agonist with a predominant action on D2 autoreceptors and with some D3 vs. D2 receptor preference. The central behavioural effects of pramipexole given subcutaneously to rats (male Wistar) and mice (Albino Swiss) are presented in this paper. Used in low doses (0.001-0.1 mg/kg), pramipexole induced locomotor hypoactivity which was antagonized by a low dose of spiperone; at higher doses (0.3, 1 mg/kg) it evoked hyperactivity which was inhibited by haloperidol, sulpiride and clozapine, but not by SCH 23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine hydrochloride). Pramipexole (0.1-1.0 mg/kg) antagonized the akinesia induced by combined pretreatment with reserpine (5 mg/kg) and alpha-methyl-p-tyrosine (250 mg/kg). Pramipexole (0.1-1 mg/kg) potentiated the hyperkinetic effect of L-DOPA (L-3,4-dihydroxyphenylalanine) (50 and 200 mg/kg, together with benserazide, 50 mg/kg) in naive and monoamine-depleted (reserpine + alpha-methyl-p-tyrosine) rats. The higher doses of pramipexole (1 and 3 mg/kg) evoked stereotypy which was antagonized by pretreatment with sulpiride or clozapine. The catalepsy induced by haloperidol, spiperone or fluphenazine was antagonized by pramipexole (1-3 mg/kg). Pramipexole (1 mg/kg) induced hypothermia in mice, which was antagonized by sulpiride. The obtained results indicate that pramipexole: (i) at low doses stimulates the dopamine D2 presynaptic autoreceptors; (ii) at higher doses stimulates dopamine D2 postsynaptic receptors. An effect on the dopamine D3 receptor cannot be excluded. At low doses pramipexole may have antipsychotic activity, and at higher ones antiparkinsonian activity.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Rogóz
Z
Z
Skuza
G
G
Kołodziejczyk
K
K
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D052160:Benzothiazoles; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000188:drug therapy; D003024:Clozapine / Q000008:administration & dosage / Q000633:toxicity; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D006220:Haloperidol / Q000008:administration & dosage / Q000633:toxicity; D007279:Injections, Subcutaneous; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D000077487:Pramipexole; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D013134:Spiperone / Q000008:administration & dosage / Q000633:toxicity; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000008:administration & dosage / Q000633:toxicity; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000978:Antiparkinson Agents; D001552:Benzazepines; D052160:Benzothiazoles; D015259:Dopamine Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493594:Drd3 protein, mouse; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D007980:Levodopa; D013134:Spiperone; D013469:Sulpiride; D000077487:Pramipexole; D003024:Clozapine; D006220:Haloperidol