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SCH 23390 antagonizes apomorphine- and ergot-induced hypothermia
Authors:E Carboni  R Longoni  S Deidda  G Di Chiara
Affiliation:1. Institute of Experimental Pharmacology and Toxicology, University of Cagliari, Cagliari, Italy;1. Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, USA;2. Lilly Research Laboratories, Eli Lilly & Co., Erl Wood Manor, United Kingdom;3. Shanghai ChemPartner, Pudong, Shanghai 201203, China;1. Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL, 60611, USA;2. Discovery Chemistry, Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN, 46285, USA;3. Neuroscience Discovery, Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN, 46285, USA;1. Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA;2. Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA;3. Department of Pharmacology, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA
Abstract:The reportedly specific D-1 dopamine (DA) receptor antagonist SCH 23390 significantly reduced the hypothermia elicited by various DA receptor agonists like apomorphine, pergolide and lisuride. When tested against equihypothermic doses of each agonist, SCH 23390 significantly reduced the hypothermia elicited by apomorphine (0.2 mg/kg s.c.) and by pergolide (0.1 mg/kg i.p.) at doses of 0.025 mg/kg s.c. Doses of 0.050 mg/kg s.c. of SCH 23390 were necessary to reduce the hypothermia elicited by 0.012 mg/kg s.c. of lisuride. Pretreatment with the specific D-2 antagonist (-)sulpiride (50 mg/kg i.p.) completely prevented the hypothermia elicited by lisuride (0.012 mg/kg i.p.), pergolide (0.1 mg/kg i.p.) and apomorphine (0.2 mg/kg s.c.) and shifted to the right the dose-response curve for agonist-induced hypothermia. A study of the interaction between 0.05 mg/kg s.c. of SCH 23390 with various doses of the agonists showed that the effectiveness of SCH 23390 in antagonizing the hypothermia was maximal towards apomorphine and least towards lisuride for which significant antagonism was observed only against the lowest dose tested (0.012 mg/kg s.c.). The reportedly specific D-1 receptor agonist SKF 38393 given in doses up to 20 mg/kg i.p. or intracerebroventricularly up to 100 micrograms failed to influence body temperature while it evoked intense grooming and stimulated motility.
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