Effects of N-methyl-D-aspartate antagonists on different measures of motion sickness in cats.
Because N-methyl-D-aspartate (NMDA) antagonists prevent cisplatin-induced emesis and NMDA receptors are in both emetic pathways and structures associated with the final common pathway for vomiting, they have the potential to be broad-spectrum antiemetics. This was evaluated by determining their effects on motion sickness in cats. The measures included the number vomiting, the number of symptom points, which reflect activity early in the final common path and the duration of the retch/vomit sequence, which reflects activity late in the path. Dextrorphan, ketamine and dextromethorphan decreased the number vomiting with the same rank order of potency as at NMDA receptors. Additional studies with 1,3-dio-tolylguaninidine (DTG) and haloperidol ruled out a role for sigma receptors. The NMDA antagonists produced a nonsignificant dose-dependent decrease in symptoms and had no effects on the duration of vomiting. They also produced motor abnormalities at the highest doses. The competitive antagonist LY 233053 also decreased the number vomiting without altering the duration. It produced a nonsignificant non-dose-dependent decrease in symptoms and had no effects on gross motor output. The results are consistent with a broad spectrum of antiemetic efficacy with at least a part of its action in the early to middle portions of the final common pathway for vomiting. Additional actions on the vestibular nuclei are possible.
Department of Pharmacology, Wright State University, Dayton, OH 45435, USA. jlucot@desire.wright.edu
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D000704:Analysis of Variance; D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D002415:Cats; D003915:Dextromethorphan / Q000627:therapeutic use; D003917:Dextrorphan / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D007649:Ketamine / Q000627:therapeutic use; D009041:Motion Sickness / Q000188:drug therapy*; D010875:Pipecolic Acids / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000627:therapeutic use
D000932:Antiemetics; D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; D003917:Dextrorphan; C066685:LY 233053; D007649:Ketamine; D003915:Dextromethorphan