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Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance
E Contreras1, L Tamayo, M Amigo
1Departamento de Ciencias Fisiológicas (Farmacología), Facultad de Ciencias Biológicas y de Recursos Naturales, Universidad de Concepción, Chile.
Abstract:
The influence of calcium channel blockers on morphine-induced analgesia and on tolerance to the chronic administration of the opiate was investigated in mice. The effects of a test dose of morphine were significantly increased by the administration of diltiazem, flunarizine, nicardipine and verapamil. In contrast, nifedipine induced an antagonistic effect. The calcium channel antagonists did not change the reaction time to thermal stimulation in mice (hot plate test). The administration of nifedipine, flunarizine and verapamil reduced the intensity of the tolerance induced by a single dose of morphine administered in a slow release preparation. Diltiazem induced a non-significant decrease of the process. The present results are in accordance with the known interaction of acute and chronic morphine administration with the intracellular calcium concentration in neurones of the central nervous system.
Insights
Calcium channel blockers influence morphine effects. Some blockers enhance pain relief, while nifedipine reduces it, impacting tolerance development in mice.
Area of Science:
- Pharmacology
- Neuroscience
- Pain Management
Background:
- Opiates like morphine are primary analgesics.
- Calcium ions play a role in neuronal signaling and opiate action.
- Tolerance to morphine limits its long-term efficacy.
Purpose of the Study:
- To investigate how calcium channel blockers affect morphine analgesia.
- To determine the impact of these blockers on morphine tolerance.
- To explore the relationship between calcium signaling and opiate effects.
Main Methods:
- Experiments were conducted using a mouse model.
- Various calcium channel blockers (diltiazem, flunarizine, nicardipine, verapamil, nifedipine) were administered.
- Morphine-induced analgesia was assessed using the hot plate test.
- Morphine tolerance was induced using a slow-release preparation.
Main Results:
- Diltiazem, flunarizine, nicardipine, and verapamil enhanced morphine analgesia.
- Nifedipine showed an antagonistic effect on morphine analgesia.
- Nifedipine, flunarizine, and verapamil reduced morphine tolerance intensity.
- Diltiazem showed a non-significant trend towards reducing tolerance.
Conclusions:
- Calcium channel blockers differentially modulate morphine's analgesic and tolerance-inducing properties.
- Results support the involvement of intracellular calcium concentration in acute and chronic morphine administration.
- Targeting calcium channels may offer strategies to manage opiate efficacy and tolerance.