- BIMU8
Drugbox
IUPAC_name = endo-N-8- methyl-8-azabicyclo [3.2.1] oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide
CAS_number = 134296-40-5
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PubChem = 5311028
DrugBank =
C=19|H=26|N=4|O=2
molecular_weight = 342.44 g/mol
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routes_of_administration =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. The main action of BIMU-8 is to increase the rate of respiration by activating an area of the brain stem known as thepre-Botzinger complex .Use
The most obvious practical use of BIMU-8 is to combine it with
opioid analgesic drugs in order to counteract the dangerousrespiratory depression which can occur when opioids are used in excessive doses. [cite journal |author=Manzke T, Guenther U, Ponimaskin E, Haller M, Dutschmann M, Schwarzacher S, Richter D |title=5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia |journal=Science |volume=301 |issue=5630 |pages=226–9 |year=2003 |pmid=12855812 |doi=10.1126/science.1084674] BIMU-8 does not affect the painkilling properties of opiates, which means that if combined with BIMU-8, large therapeutic doses of opiates could theoretically be given tohuman s without risking a decrease in breathing rate. Studies have shown BIMU-8 to be effective inrat s at counteracting the respiratory depression caused by the potent opioidfentanyl , [Wang X, Dergacheva O, Kamendi H, Gorini C, Mendelowitz D. 5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function. "Hypertension". 2007 Aug;50(2):368-76. PMID 17576856] 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 5HT4 agonists in learning and memory, [cite journal |author=Meneses A, Hong E |title=Effects of 5-HT4 receptor agonists and antagonists in learning |journal=Pharmacol Biochem Behav |volume=56 |issue=3 |pages=347–51 |year=1997 |pmid=9077568 |doi=10.1016/S0091-3057(96)00224-9] 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 5HT4 agonists such as
mosapride andtegaserod (the only5HT4 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 5HT4 agonistzacopride does inhibit respiratory depression in a similar manner to BIMU-8. [Meyer LC, Fuller A, Mitchell D. Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats. "American Journal of Physiology. Regulatory, Integrative and Comparative Physiology". 2006 Feb;290(2):R405-13. PMID 16166206]This suggests that either the anti-respiratory depression action is mediated via a specific subtype of the 5HT4 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 5HT4 binding compared to other 5HT4 agonists.References
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