of nalmefene in the treatment of alcohol dependence, as well as summarizing its pharmacological properties. Ethanol increases the release of endogenous opioids, such as β-endorphin, a μ-opioid receptor agonist; and dynorphin, a κ-opioid receptor agonist. Preclinical data suggest that nalmefene acts as an antagonist at the μ-opioid receptor and a partial agonist at the κ-opioid receptor, and reduces ethanol
of ethanol. We propose that reducing activity, genetically or pharmacologically by ethanol binding to the C1 domain of Munc13-1/Dunc13, promotes a homeostatic response that leads to ethanol tolerance.
-clamp recordings and pharmacological manipulation. Ethanol (300 mM) induced a decrease in the CS-evoked pause in simple spike (SS) firing and in the amplitude of the afterhyperpolarization (AHP) under current clamp conditions. Under voltage-clamp conditions, ethanol significantly decreased the area under the curve (AUC) and the number of CS spikelets, without changing the spontaneous frequency
expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal". The Journal of Neuroscience. 23 (37): 11711–24. doi:10.1523/JNEUROSCI.23-37-11711.2003. PMC6740939. PMID14684873. 21. ^ Idemudia SO, Bhadra S, Lal H (June 1989). "The pentylenetetrazol-like interoceptive stimulus produced by ethanol withdrawal is potentiated by bicuculline and picrotoxinin