Chemistry:BMB-101

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BMB-101 is a serotonin 5-HT2C receptor agonist which is under development for the treatment of absence epilepsy, binge-eating disorder, Dravet syndrome, Lennox–Gastaut syndrome, Pitt–Hopkins syndrome, Prader–Willi syndrome, and Rett syndrome.[1][2][3][4][5] It is taken orally.[1]

Pharmacology

Pharmacodynamics

BMB-101 acts as a highly selective biased agonist of the serotonin 5-HT2C receptor.[1][6][3][5] It has greater that 100-fold selectivity for the serotonin 5-HT2C receptor over other serotonin receptors, including the serotonin 5-HT2A and 5-HT2B receptors.[3][5] BMB-101 shows functional selectivity at the serotonin 5-HT2C receptor for activation of Gq signaling with minimal β-arrestin recruitment.[6][3][5] This in turn appears to minimize receptor desensitization and development of tolerance.[6][3] Due to its much greater selectivity for the serotonin 5-HT2C receptor, BMB-101 is not expected to possess the psychedelic effects or cardiotoxicity that have been associated with existing drugs like fenfluramine and lorcaserin at therapeutic or supratherapeutic doses.[3][4][5] In accordance with its mechanism of action, BMB-101 produces anticonvulsant effects in animals.[4]

The activation of serotonin 5-HT2C receptors has been shown to reduce epileptic seizure activity by inhibiting T-type calcium channels (Cav3).[7] These calcium channels facilitate high frequency burst firing in principal neurons of the subiculum. This firing pattern is upregulated following status epilepticus, with these hyperactive neurons often serving as the initiation point for seizures.[8][9][10]

Chemistry

Lumocaserin structure.

The exact chemical structure of BMB-101 does not yet appear to have been disclosed.[1][2][11] However, it is known to be a 2-phenylcyclopropylmethylamine (PCPMA) derivative and to share structural commonalities with tranylcypromine.[5][11] Moreover, lumocaserin (INN; CAS no. 1656330-84-5), a serotonin 5-HT2C receptor agonist of the PCPMA scaffold described as an anticonvulsant,[12] has been patented by Bright Minds Biosciences-associated researchers including Alan Kozikowski and Jianjun Cheng.[13][14] Lumocaserin's INN was registered in January 2026.[12] The pharmacology and synthesis of lumocaserin have been described.[15] Various structurally related serotonin 5-HT2C receptor agonists have also been studied and described by Kozikowski and colleagues.[15][16]

Research

BMB-101 is under development by Bright Minds Biosciences.[1][2] As of January 2026, it is in phase 2 clinical trials for the treatment of absence epilepsy, Dravet Syndrome, Lennox–Gastaut syndrome, Pitt–Hopkins syndrome, Prader–Willi syndrome, and Rett syndrome.[1][2] It is or was also under development for the treatment of binge-eating disorder and opioid use disorder, but no recent development has been reported for these indications.[1][2]

The drug has been found to increase REM sleep time by 90% (from 56 minutes to 107 minutes) without altering total sleep duration (9.1 hours vs. 8.9 hours) in people with absence seizures in a clinical study.[17]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "BMB 101". 23 October 2024. https://adisinsight.springer.com/drugs/800065004. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "Delving into the Latest Updates on BMB-101 with Synapse". 29 October 2024. https://synapse.patsnap.com/drug/5f9c9ec925e648cdab118b9cd71dc86e. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 "BMB-101: A selective 5-HT2C agonist for the treatment of rare epilepsies". Seventeenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII), Madrid, Spain 5–8 May 2024. May 2024. https://brightmindsbio.com/wp-content/uploads/2024/10/BMB-101-Eilat-conference-2024-poster.pdf. 
  4. ↑ 4.0 4.1 4.2 "Selective 5-HT2C Agonists for the Treatment of Rare Epileptic Disorders". Society for Neuroscience 2024 Annual Meeting (Chicago), Satellite NIH Forum, October 5–9. October 2024. https://brightmindsbio.com/wp-content/uploads/2024/10/5-HT2C-ETSP-poster-final.pdf. 
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 "Bright Minds Investor Deck". Bright Minds Biosciences Inc.. September 2024. https://brightmindsbio.com/wp-content/uploads/2024/09/BMB_investor_deck_September.pdf. 
  6. ↑ 6.0 6.1 6.2 "Bright Minds Biosciences Launches Phase 2 Trial of BMB-101 for Epilepsy". 14 September 2024. https://synapse.patsnap.com/article/bright-minds-biosciences-launches-phase-2-trial-of-bmb-101-for-epilepsy. 
  7. ↑ "Serotonin Regulates the Firing of Principal Cells of the Subiculum by Inhibiting a T-type Ca2+ Current". Frontiers in Cellular Neuroscience 11: 60. 2017. doi:10.3389/fncel.2017.00060. PMID 28326015. 
  8. ↑ "Synaptic contributions to focal and widespread spatiotemporal dynamics in the isolated rat subiculum in vitro". The Journal of Neuroscience 24 (24): 5525–36. June 2004. doi:10.1523/JNEUROSCI.0309-04.2004. PMID 15201325. 
  9. ↑ "Upregulation of a T-type Ca2+ channel causes a long-lasting modification of neuronal firing mode after status epilepticus". The Journal of Neuroscience 22 (9): 3645–55. May 2002. doi:10.1523/JNEUROSCI.22-09-03645.2002. PMID 11978840. 
  10. ↑ "On the origin of interictal activity in human temporal lobe epilepsy in vitro". Science 298 (5597): 1418–1421. 2002. doi:10.1126/science.1076510. PMID 12434059. Bibcode: 2002Sci...298.1418C. 
  11. ↑ 11.0 11.1 "Overview of Bright Minds Biosciences: Pioneering Serotonin Pharmacology". 2025 AES Annual Meeting, December 5–9, Atlanta, Georgia. 7 December 2025. https://brightmindsbio.com/wp-content/uploads/2025/12/1.-Overview-of-Bright-Minds-Biosciences.-Pioneering-Serotonin-Pharmacology-_compressed.pdf. 
  12. ↑ 12.0 12.1 "International Nonproprietary Names for Pharmaceutical Substances (INN)". WHO Drug Information 39 (4): 1221. 2025. https://cdn.who.int/media/docs/default-source/international-nonproprietary-names-(inn)/pl134.pdf. 
  13. ↑ "Cyclopropylmethanamines as selective 5-HT(2C) receptor agonists". 27 January 2016. https://patents.google.com/patent/US10407381B2/en. 
  14. ↑ "Lumocaserin". https://pubchem.ncbi.nlm.nih.gov/compound/118733818. 
  15. ↑ 15.0 15.1 "Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents". J Med Chem 58 (4): 1992–2002. February 2015. doi:10.1021/jm5019274. PMID 25633969. "Routes to the 5-fluoro compounds are depicted in Scheme 2 [...] These intermediates were separated using chiral preparative HPLC and then deprotected with HCl in diethyl ether to give both (−)- and (+)-enantiomers of compound 16a−16d. [...] Scheme 2. Synthesis of 5-Fluoro Compoundsa [...] Table 4. Efficacy and Selectivity Data of Compound 16a−16da,b [...] (+)-16a [...] Compound (+)-16a, bearing an n-propyl group, displayed an EC50 value of 11 nM at 5-HT2C and was 9-fold more potent than its 5-chloro analogue (+)-13b (EC50 = 103 nM). It showed a high degree of selectivity over 5-HT2B (EC50 = 1994 nM) and 5-HT2A (no activity). [...] General Method C: Deprotection of N-Boc-Amines to Afford HCl Salts (13a, 13b, 13e−13g, 13i−13n, and 16a−16d). [...]". 
  16. ↑ "Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications". J Med Chem 60 (14): 6273–6288. July 2017. doi:10.1021/acs.jmedchem.7b00584. PMID 28657744. 
  17. ↑ Meglio, Marco (16 January 2026). "BMB-101 Heads for Registrational Trials Following Positive Phase 2 Data in Absence Seizures, Developmental Encephalopathies". https://www.neurologylive.com/view/bmb-101-registrational-trials-following-positive-phase-2-data-absence-seizures-developmental-encephalopathies. "Outside of seizure control, BMB-101 also demonstrated a positive impact on outcomes of sleep in treated patients. Treatment with BMB-101 increased REM sleep by approximately 90% (from 56.2 minutes at baseline to 106.7 minutes) without meaningfully changing total sleep duration (9.1 vs 8.9 hours), indicating that REM gains were independent of overall sleep time." 



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