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Exploring μ-Opioid Receptor Splice Variants as a Specific Molecular Target for New Analgesics
Hirokazu Mizoguchi1, Hideaki Fujii2
1Department of Physiology and Anatomy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Abstract:
Since a μ-opioid receptor gene containing multiple exons has been identified, the variety of splice variants for μ-opioid receptors have been reported in various species. Amidino-TAPA and IBNtxA have been discovered as new analgesics with different pharmacological profiles from morphine. These new analgesics show a very potent analgesic effect but do not have dependence liability. Interestingly, these analgesics show the selectivity to the morphine-insensitive μ-opioid receptor splice variants. The splice variants, sensitive to these new analgesics but insensitive to morphine, may be a better molecular target to develop the analgesics without side effects.
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