Behavioural analysis of changes in nociceptive thresholds produced by remoxipride in sheep and rats.
The antinociceptive potential of remoxipride was investigated in sheep and rats with concurrent motor function assessments. Previous studies of sheep given intravenous remoxipride have revealed increases in mechanical nociceptive thresholds. Here, further investigation in sheep demonstrated elevated thermal nociceptive thresholds with no effect on subjectively assessed sedation or motor impairment scores. However, in rats, the dose of remoxipride (100 mg/kg i.p.) required to produce nociceptive thresholds similar to those elicited by morphine (30 mg/kg i.p.), itself reduced rotarod performance. Medetomidine (200 micrograms/kg i.p.) evoked sedation without influencing rotarod performance or antinociception. The antinociceptive, motor deficit and cataleptogenic actions of remoxipride were similar to those induced by two other dopamine antagonists, haloperidol (5 mg/kg) and raclopride (16 mg/kg i.p). Tocainide (100 mg/kg i.p.) induced thermal antinociception with normal rotarod performance and no catalepsy suggesting that Na+ channel blockade by remoxipride is not responsible for the changes in nociceptive thresholds. This study emphasizes the importance of motor function assessment during acute antinociceptive testing.
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Department of Clinical Veterinary Science, University of Bristol, UK.
Waterman
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Kilpatrick
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D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D020926:Medetomidine; D009043:Motor Activity / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017330:Remoxipride / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D016037:Single-Blind Method; D013045:Species Specificity; D016677:Tocainide / Q000008:administration & dosage / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000889:Anti-Arrhythmia Agents; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D017330:Remoxipride; D016677:Tocainide; D020926:Medetomidine