BIMU8

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Chemical compound

title: "BIMU8" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["respiratory-agents", "antidotes", "serotonin-receptor-agonists", "tropanes", "benzimidazoles", "ureas", "lactams", "isopropyl-compounds"] description: "Chemical compound" topic_path: "general/respiratory-agents" source: "https://en.wikipedia.org/wiki/BIMU8" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical compound ::

| verifiedrevid = 447613417 | IUPAC_name = N-[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]-2-oxo-3-(propan-2-yl)-2,3-dihydro-1H-benzimidazole-1-carboxamide hydrochloride | image = BIMU8.svg | tradename = | pregnancy_AU = | pregnancy_US = | legal_AU = | legal_CA = | legal_UK = | legal_US = | CAS_number_Ref = | CAS_number = 134296-40-5 | PubChem = 5311028 | DrugBank_Ref = | ChemSpiderID_Ref = | ChemSpiderID = 4470566 | chemical_formula=· HCl | smiles = Cl.O=C2N(c1ccccc1N2C(=O)NC4C[C@H]3N(C)C@HC4)C(C)C | StdInChI_Ref = | StdInChI = 1S/C19H26N4O2.ClH/c1-12(2)22-16-6-4-5-7-17(16)23(19(22)25)18(24)20-13-10-14-8-9-15(11-13)21(14)3;/h4-7,12-15H,8-11H2,1-3H3,(H,20,24);1H/t13?,14-,15+; | StdInChIKey_Ref = | StdInChIKey = NQYXXIUVFVOJCX-XZPOUAKSSA-N

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 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.

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. 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.

Other activity

Along with several other 5-HT4 ligands, BIMU-8 was also found to possess significant affinity for the sigma receptors, acting as a σ2 antagonist. It is unclear as yet what contribution this additional activity makes to the pharmacological profile of BIMU-8 and other 5-HT4 ligands that also show sigma affinity.

References

References

  1. (August 1990). "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.
  2. (March 1991). "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.
  3. (July 2003). "5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia". Science.
  4. (August 2007). "5-Hydroxytryptamine 1A/7 and 4alpha receptors differentially prevent opioid-induced inhibition of brain stem cardiorespiratory function". Hypertension.
  5. (March 1997). "Effects of 5-HT4 receptor agonists and antagonists in learning". Pharmacology, Biochemistry, and Behavior.
  6. (September 2005). "The 5-hydroxytryptamine 4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression". Clinical Pharmacology and Therapeutics.
  7. (February 2006). "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.
  8. (October 1994). "[3H]RS-23597-190, a potent 5-hydroxytryptamine4 antagonist labels sigma-1 but not sigma-2 binding sites in guinea pig brain". The Journal of Pharmacology and Experimental Therapeutics.
  9. (May 1997). "Regulation of [3H]norepinephrine release from guinea pig hippocampus by sigma2 receptors". European Journal of Pharmacology.
  10. (June 2001). "Trishomocubanes: novel sigma-receptor ligands modulate amphetamine-stimulated [3H]dopamine release". European Journal of Pharmacology.

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respiratory-agentsantidotesserotonin-receptor-agoniststropanesbenzimidazolesureaslactamsisopropyl-compounds