Mechanisms of Morphine Enhancement of Spontaneous Seizure Activity
2007; Lippincott Williams & Wilkins; Volume: 105; Issue: 6 Linguagem: Inglês
10.1213/01.ane.0000287675.15225.0b
ISSN1526-7598
AutoresEhsan Saboory, Miron Derchansky, Mohammed Ismaili, S. S. Jahromi, Richard Brull, Peter L. Carlen, Hossam El Beheiry,
Tópico(s)Pharmacological Receptor Mechanisms and Effects
ResumoIn Brief BACKGROUND: High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. METHODS: Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. RESULTS: Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 μM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 μM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective μ and κ opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, δ opioid receptor ligands did not have an effect. CONCLUSIONS: The proseizure effect of morphine is mediated through selective stimulation of μ and κ opiate receptors but not the activation of the δ receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting. IMPLICATIONS: In this in vitro study using mouse hippocampus, the proseizure effect of morphine was mediated by μ and κ opioid receptors.
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