Chemistry:PRAX-114

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PRAX-114 is a neurosteroid and GABAA receptor positive allosteric modulator which is under development for the treatment of major depressive disorder, essential tremor, depressive disorders, and epilepsy.[1][2][3][4][5] It was also under development for the treatment of post-traumatic stress disorder (PTSD), but development for this indication was discontinued.[1] The drug is taken by mouth.[3][1]

PRAX-114 is described as an extrasynaptic-preferring GABAA receptor positive allosteric modulator with a wider separation between antidepressant-like activity and sedative effects in preclinical research than related drugs like zuranolone.[4][3][5][6] It has 10.5-fold preference for potentation of extrasynaptic GABAA receptors over synaptic GABAA receptors in vitro.[4] Hence, the drug is theorized to have improved tolerability.[4][5][6] PRAX-114 shows antidepressant-like, anxiolytic-like, and, at higher doses, sedative effects in animals.[4][5][6]

As of March 2023, PRAX-114 is in phase 2/3 clinical trials for major depressive disorder and phase 2 clinical trials for essential tremor.[1][2][3] No recent development has been reported for treatment of depressive disorders and epilepsy.[1] In a June 2023 literature review, it was reported that PRAX-114 had failed to show effectiveness in the treatment of major depressive disorder in a phase 2/3 trial and that there were no further plans to develop PRAX-114 for treatment of psychiatric disorders.[3] The drug is or was under development by Praxis Pharmaceuticals.[1][2][3] Aside from being a small molecule and neurosteroid, the chemical structure of PRAX-114 does not seem to have been disclosed.[3][1][2]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "PRAX 114". AdisInsight. Springer Nature Switzerland AG. 28 March 2023. https://adisinsight.springer.com/drugs/800051916. 
  2. ↑ 2.0 2.1 2.2 2.3 "Delving into the Latest Updates on PRAX-114 with Synapse". 19 October 2024. https://synapse.patsnap.com/drug/b1ef8690d8394cb78820d2129ca843f1. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 "Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder". Transl Psychiatry 13 (1): 228. June 2023. doi:10.1038/s41398-023-02514-2. PMID 37365161. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 "Clinical specificity profile for novel rapid acting antidepressant drugs". Int Clin Psychopharmacol 38 (5): 297–328. September 2023. doi:10.1097/YIC.0000000000000488. PMID 37381161. 
  5. ↑ 5.0 5.1 5.2 5.3 "PRAX-114 is a Novel Extrasynaptic GABA-A Receptor Preferring Positive Allosteric Modulator With a Wide Separation Between a Translational Biomarker Signature Associated With Antidepressant-Like Activity, and Sedative Effects". Biological Psychiatry (Elsevier BV) 89 (9): S204. 2021. doi:10.1016/j.biopsych.2021.02.517. ISSN 0006-3223. 
  6. ↑ 6.0 6.1 6.2 "P140. Preference for Extrasynaptic GABAA Receptors Conveys a Wider Therapeutic Window Between Anxiolytic and Sedative-Like Effects in Rats for the Positive Allosteric Modulator, PRAX-114, Compared With Zuranolone". Biological Psychiatry (Elsevier BV) 91 (9): S143–S144. 2022. doi:10.1016/j.biopsych.2022.02.374. ISSN 0006-3223. 



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