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.[2][3][1][4][5] It was also under development for the treatment of post-traumatic stress disorder (PTSD), but development for this indication was discontinued.[2] The drug is taken by mouth.[1][2]
| Clinical data | |
|---|---|
| Other names | PRAX114 |
| Routes of administration | Oral[1][2] |
| Drug class | Neurosteroid; GABAA receptor positive allosteric modulator[1][2] |
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][1][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.[2][3][1] No recent development has been reported for treatment of depressive disorders and epilepsy.[2] 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.[1] The drug is or was under development by Praxis Pharmaceuticals.[2][3][1] Aside from being a small molecule and neurosteroid, the chemical structure of PRAX-114 does not seem to have been disclosed.[1][2][3]
References
edit- ^ a b c d e f g h i Cutler AJ, Mattingly GW, Maletic V (June 2023). "Understanding the mechanism of action and clinical effects of neuroactive steroids and GABAergic compounds in major depressive disorder". Transl Psychiatry. 13 (1): 228. doi:10.1038/s41398-023-02514-2. PMC 10293235. PMID 37365161.
- ^ a b c d e f g h i "PRAX 114". AdisInsight. Springer Nature Switzerland AG. 28 March 2023. Retrieved 21 October 2024.
- ^ a b c d "Delving into the Latest Updates on PRAX-114 with Synapse". Synapse. 19 October 2024. Retrieved 21 October 2024.
- ^ a b c d e Scala M, Fanelli G, De Ronchi D, Serretti A, Fabbri C (September 2023). "Clinical specificity profile for novel rapid acting antidepressant drugs". Int Clin Psychopharmacol. 38 (5): 297–328. doi:10.1097/YIC.0000000000000488. PMC 10373854. PMID 37381161.
- ^ a b c d Hughes Z, Scott L, Kahlig K, Wittmann M (2021). "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. 89 (9). Elsevier BV: S204. doi:10.1016/j.biopsych.2021.02.517. ISSN 0006-3223.
- ^ a b c Hughes Z, Scott L, Kahlig K, Wittmann M (2022). "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. 91 (9). Elsevier BV: S143–S144. doi:10.1016/j.biopsych.2022.02.374. ISSN 0006-3223.