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Anticonvulsant effect of morphine and morphine-like analgesics in Mongolian gerbils
Abstract:
The effect of morphine, fentanyl, pethidine and pentazocine was studied in gerbils against air blast-induced seizures. Major, generalized seizures were suppressed by morphine (ED50 = 4.0 mg/kg s.c.), fentanyl (ED50 = 64 micrograms/kg s.c.), and pethidine (ED50 = 2.4 mg/kg s.c.), but not by pentazocine. The anticonvulsant effect of the drugs was lost with higher doses which partly induced spontaneous convulsions. The comparatively high potency of pethidine in this model may point to a role of other receptors (or processes) besides the mu-receptor for this drug.
Insights
Morphine, fentanyl, and pethidine effectively suppressed seizures in gerbils. Higher doses of these opioids induced convulsions, suggesting complex receptor interactions beyond mu-opioid receptors for pethidine.
Area of Science:
- Neuroscience
- Pharmacology
- Seizure Disorders
Background:
- Opioid analgesics are commonly used for pain management.
- Understanding their effects on seizure activity is crucial for patient safety.
- Gerbils serve as a model for studying generalized seizures.
Purpose of the Study:
- To investigate the anticonvulsant effects of morphine, fentanyl, pethidine, and pentazocine.
- To determine the efficacy of these opioids in suppressing air blast-induced seizures in gerbils.
- To explore dose-dependent effects and potential mechanisms of action.
Main Methods:
- Gerbils were subjected to air blast-induced seizures.
- Various doses of morphine, fentanyl, pethidine, and pentazocine were administered subcutaneously.
- Anticonvulsant activity and dose-response relationships (ED50) were evaluated.
- Higher doses were tested to observe toxicity and pro-convulsant effects.
Main Results:
- Morphine (ED50 = 4.0 mg/kg), fentanyl (ED50 = 64 µg/kg), and pethidine (ED50 = 2.4 mg/kg) demonstrated significant suppression of generalized seizures.
- Pentazocine did not exhibit anticonvulsant properties in this model.
- Elevated doses of the effective opioids led to spontaneous convulsions, indicating a loss of anticonvulsant effect.
- Pethidine's high potency suggests involvement of non-mu-opioid pathways.
Conclusions:
- Morphine, fentanyl, and pethidine possess potent anticonvulsant activity against air blast-induced seizures in gerbils.
- Pentazocine is ineffective as an anticonvulsant in this seizure model.
- Dose escalation of these opioids can paradoxically induce seizures, highlighting a narrow therapeutic window.
- Pethidine's efficacy may involve interactions with receptors or processes beyond the mu-opioid receptor.