Effects on body temperature in mice differentiate between dopamine D2 receptor agonists with high and low efficacies.
The effects of different dopamine (DA) D2 receptor agonists and the DA D2 receptor antagonist, emonapride, on body temperature were studied in male mice. The aim of the study was to test whether DA D2 receptor agonists ranging from full agonists to agonists with low efficacy could be differentiated by means of their effect on body temperature. Talipexole induced a marked hypothermia (maximum decrease of 6.5 degrees C). Apomorphine, quinelorane, (+)-4-propyl-9-hydroxy-naphtoxazine((+)-PHNO), and (-)-N-n-propylnorapomorphine ((-)-NPA) induced a maximum hypothermia of 3.5-4.1 degrees C. Quinpirole and (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) induced a less pronounced hypothermia (1.7 and 1.5 degrees C), and preclamol ((-)-3-PPP), terguride and 3-(4-(4-phenyl-1,2,3,6-tetrahydropyridyl)-(1))-butyl)-indole (EMD 23448) had no or only a slight effect. Emonapride induced significant hyperthermia at high doses. Apomorphine-, quinelorane- and talipexole-induced hypothermia was reversed by terguride and preclamol, whereas EMD 23448 partially reversed the apomorphine-induced hypothermia. The alpha 2-adrenoceptor antagonist, idazoxan, partly reversed the effect of talipexole. Quinpirole had no effect on the hypothermic effect of the above-mentioned agonists. Pretreatment with the catecholamine synthesis inhibitor, alpha-methyl-m-tyrosine, increased significantly the hypothermic response to quinpirole, whereas the effect of quinelorane was unchanged. It is suggested that the effect of DA D2 agonists on body temperature in mice can be used to differentiate between agonists with different efficacies.(ABSTRACT TRUNCATED AT 250 WORDS)
Sánchez
C
C
Pharmacological Research, H. Lundbeck A/S, Copenhagen-Valby, Denmark.
Arnt
J
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2