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BIMU-8 is a drug which acts as a 5-HT4 receptor selective agonist. BIMU-8 was one of the first compounds of this class.〔Turconi M, Nicola M, Quintero MG, Maiocchi L, Micheletti R, Giraldo E, Donetti A. Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives as highly potent 5-HT3 receptor antagonists. ''Journal of Medicinal Chemistry''. 1990 Aug;33(8):2101-8. PMID 1695682〕〔Dumuis A, Sebben M, Monferini E, Nicola M, Turconi M, Ladinsky H, Bockaert J. Azabicycloalkyl benzimidazolone derivatives as a novel class of potent agonists at the 5-HT4 receptor positively coupled to adenylate cyclase in brain. ''Naunyn-Schmiedeberg's Archives of Pharmacology''. 1991 Mar;343(3):245-51. PMID 1650917〕 The main action of BIMU-8 is to increase the rate of respiration by activating an area of the brain stem known as the pre-Botzinger complex. == Use == The most obvious practical use of BIMU-8 is to combine it with opioid analgesic drugs in order to counteract the dangerous respiratory depression which can occur when opioids are used in excessive doses. BIMU-8 does not affect the pleasurable or painkilling properties of opiates, which means that if combined with BIMU-8, large therapeutic doses of opiates could theoretically be given to humans without risking a decrease in breathing rate. Studies have shown BIMU-8 to be effective in rats at counteracting the respiratory depression caused by the potent opioid fentanyl, which has caused many accidental deaths in humans. However, no human trials of BIMU-8 have yet been carried out. Other studies have suggested a role for 5-HT4 agonists in learning and memory, and BIMU-8 was found to increase conditioned responses in mice, so this drug might also be useful for improving memory in humans. Interestingly some other selective 5-HT4 agonists such as mosapride and tegaserod (the only 5-HT4 agonists currently licensed for use in humans) have been found not to reduce respiratory depression.〔Lotsch J, Skarke C, Schneider A, Hummel T, Geisslinger G. The 5-hydroxytryptamine 4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression. ''Clinical Pharmacology and Therapeutics''. 2005 Sep;78(3):278-87.〕 On the other hand, another 5-HT4 agonist, zacopride, does inhibit respiratory depression in a similar manner to BIMU-8. This suggests that either the anti-respiratory depression action is mediated via a specific subtype of the 5-HT4 receptor which is activated by BIMU-8 and zacopride, but not by mosapride or tegaserod, or alternatively there may be functional selectivity involved whereby BIMU-8 and zacopride produce a different physiological response following 5-HT4 binding compared to other 5-HT4 agonists. Another alternative to this is that the 5-HT4 agonist currently available for use in humans do not have great enough potency or bioavailability in the brain to elicit the same effects.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「BIMU8」の詳細全文を読む スポンサード リンク
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