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Published on: July 29, 2014
A study of tolerance to apomorphine
J L Montastruc1, M E Llau, J M Senard
1Faculté de Médecine, Inserm U 317, Toulouse, France.
British Journal of Pharmacology
|March 1, 1996
Summary
This study shows that dogs develop tolerance to apomorphine's effects on blood pressure, temperature, and vomiting. Tolerance develops faster for cardiovascular and emetic effects than for hypothermic effects.
Area of Science:
- Pharmacology
- Neuroscience
- Veterinary Medicine
Background:
- Apomorphine is a dopamine receptor agonist with various physiological effects.
- Understanding tolerance to apomorphine is crucial for its therapeutic applications and managing side effects.
Purpose of the Study:
- To investigate the development of tolerance to the cardiovascular, thermoregulatory, and emetic effects of apomorphine.
- To determine the time course of tolerance to repeated apomorphine administration in anesthetized dogs.
Main Methods:
- Four groups of chloralose-anesthetized dogs received an initial intravenous bolus of apomorphine (200 µg/kg) or saline.
- Subsequent apomorphine administration occurred at 30, 120, or 720 minutes to assess tolerance.
- Changes in blood pressure, heart rate, rectal temperature, respiratory rate, plasma noradrenaline, and emesis were monitored.
Main Results:
- The first apomorphine dose significantly decreased blood pressure and temperature, increased heart rate, and caused emesis in 71% of dogs.
- Tolerance to cardiovascular effects (blood pressure, heart rate) developed within 30 minutes.
- Tolerance to hypothermic and emetic effects showed a slower onset, with significant differences observed at 120 and 720 minutes.
Conclusions:
- Tolerance to apomorphine's cardiovascular, hypothermic, and emetic effects was demonstrated.
- The time course of tolerance varies, with faster development for cardiovascular and emetic effects compared to hypothermic effects.
- These findings suggest tissue-specific regulation of dopamine D2 receptors in response to repeated apomorphine exposure.
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