Interdisciplinary studies have used in vitro, animal and human studies to elucidate mechanisms of opioid action and develop new therapeutic modalities. Electrophysiological studies of Ca2+ channels revealed that N channels are necessary for monosynaptic transmission, and L channels are important in spontaneous synaptic transmission. Kappa opioids and conotoxin block separate Ca2+ channels. In related studies, hydrophobicity of etorphine congeners correlated with mu opioids receptor binding affinity, suggesting drug sequestration within the lipid membrane. DADLE, a delta opioid receptor ligand, markedly prolonged organ survival time in a canine multiorgan preservation preparation (e.g., liver survival increased from 2 to 46 h) even though DADLE was largely eliminated within 2 h. Rat experiments demonstrated that inhibiting nitric oxide synthase with nitroarginine or the monomethyl ester of arginine ameliorated precipitated opioid abstinence, suggesting a novel withdrawal treatment. In other rodent studies, morphine reduced the expression of cell surface antigens on T-lymphocytes in mice, indicating immunosuppression by the opioid. A human study assessed the interactions of the Ca2+ channel antagonist verapamil and morphine. subjective effects of morphine were antagonized by verapamil, and verapamil potentiated the effect of morphine on pain threshold. In another human study, spectral analysis of the electroencephalogram in polydrug abusers revealed that morphine attenuates a nondrug-induced increase in delta power and produces an increase in slow frequency alpha power, which positively correlated euphoria.
