Mechanism of antiemetic action of penfluridol in the dog
| Autor: | Hsheng K. Lee, Pao M. Chung, Shih C. Wang |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Male
Apomorphine medicine.drug_class Administration Oral Pharmacology Penfluridol Levodopa Dogs Piperidines medicine Antiemetic Animals Injections Intraventricular Medulla Oblongata business.industry Dopamine antagonist Epinephrine Pilocarpine Injections Intravenous Morphine Vomiting Antiemetics Female medicine.symptom business Drug Antagonism medicine.drug |
| Zdroj: | European journal of pharmacology. 53(1) |
| ISSN: | 0014-2999 |
| Popis: | In conscious mongrel dogs, the 50% protective dose (PD50) of intracerebroventricular (i.c.v., 4th ventricle) and oral (p.o.) penfluridol against emesis induced by apomorphine 0.01 mg/kg i.v. was 0.7 ng/kg and 1.5 μg/kg, respectively, with a ratio of about 1 to 2,000. Another striking feature of penfluridol as an antiemetic was its long duration of action. With a moderate oral dose, e.g. 10 μg/kg, the protective effect could last several days. Penfluridol, 1 mg/kg p.o., was extremely effective in raising the i.v. threshold emetic dose of apomorphine (1 mg/kg), levodopa (20 mg/kg) or Hydergine (0.09 mg/kg). With such a dose of penfluridol, however, the emetic threshold of oral copper sulfate was not raised. Furthermore, penfluridol had no effect in preventing vomiting induced by Veriloid, peruvoside and pilocarpine. These findings suggest that the primary site of the antiemetic property of penfluridol is a selective action on the chemoceptive emetic trigger zone of the medulla. Penfluridol afforded only moderate protection against vomiting induced by epinephrine, emetine or sodium salicylate, and was not effective against that induced by ouabain, acetylstrophanthidin, morphine, and nicotine. Since these emetic agents act principally through the trigger zone, this may imply that penfluridol administration is not equivalent to surgical ablation of this area. In addition, penfluridol only raised the threshold of emesis induced by apomorphine, levodopa and Hydergine, known to stimulate specifically the dopamine receptors. Furthermore, levodopa at a non-emetic i.v. dose was markedly effective in antagonizing the antiapomorphine action of penfluridol. These results suggest that penfluridol exerts its antiemetic action through an antidopaminergic activity. |
| Databáze: | OpenAIRE |
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