Tianeptine/naloxone (developmental code names TNX-601, TNX-601-CR, TNX-601-ER), or naloxone/tianeptine, is an extended-release combination of tianeptine, an atypical μ-opioid receptor agonist, and naloxone, an orally inactive μ-opioid receptor antagonist, which was under development for the treatment of major depressive disorder, post-traumatic stress disorder (PTSD), and neurocognitive dysfunction associated with corticosteroid use but was never marketed.[1][2][3][4][5]
 | |
 | |
| Combination of | |
|---|---|
| Tianeptine | Atypical μ-opioid receptor agonist |
| Naloxone | Orally inactive μ-opioid receptor antagonist |
| Clinical data | |
| Other names | Naloxone/tianeptine; Tianeptine oxalate/naloxone; Naloxone/tianeptine oxalate; Tianeptine hemioxalate/naloxone; Naloxone/tianeptine hemioxalate; TNX-601; TNX601; TNX-601 CR; TNX-601-CR; TNX-601 ER; TNX-601-ER |
| Routes of administration | Oral |
Whereas tianeptine is marketed widely throughout Europe, Asia, and Latin America but is not available in the United States or the United Kingdom, tianeptine/naloxone was under development for registration in the United States and other countries.[1][3][4] In addition, whereas tianeptine has a short duration of action and requires administration three times per day, tianeptine/naloxone was developed as an extended-release formulation with enhanced pharmacokinetics suitable for once-daily administration.[3][1] The combination formulation employs tianeptine as the oxalate salt, which is said to have improved physicochemical properties for use in the extended-release formulation compared to the amorphous tianeptine sodium that is used in immediate-release tianeptine-only formulations.[3][1] Naloxone is used in misuse-resistant oral drug formulations as it is inactive if taken orally but becomes active if oral tablets are crushed and administered parenterally, such as by injection.[6][4]
Tianeptine/naloxone reached phase 2 clinical trials for major depressive disorder and phase 1 clinical trials for post-traumatic stress disorders and cognition dysfunction related to corticosteroid use prior to the discontinuation of its development.[1][2] Its development was discontinued for all indications in October 2023 due to lack of effectiveness for major depressive disorder in a phase 2 clinical trial.[1][7]
References
edit- ^ a b c d e f "Naloxone/tianeptine - Tonix Pharmaceuticals". AdisInsight. 2 November 2023. Retrieved 21 October 2024.
- ^ a b "Delving into the Latest Updates on Tianeptine Oxalate(Tonix Pharmaceuticals, Inc.) with Synapse". Synapse. 19 September 2024. Retrieved 21 October 2024.
- ^ a b c d "CNS Summit 2021: Abstracts of Poster Presentations: TNX-601 CR*: A ONCE-DAILY FORMULATION OF TIANEPTINE IN DEVELOPMENT FOR THE TREATMENT OF MAJOR DEPRESSIVE DISORDER IN THE UNITED STATES". Innovations in Clinical Neuroscience. 18 (10-12 Suppl 1): S5–S16. 2021. PMC 8752122.
- ^ a b c Sullivan GM, Hsu DT, Peters A, Peters P, Fogarty S, Kiu R, Meibohm B, Lederman S. TNX-601 CR*: a Once-Daily Formulation of Tianeptine in Development for the Treatment of Major Depressive Disorder (PDF). CNS Summit 2021, Nov 7-10, 2021.
- ^ "Tonix Pharmaceuticals Announces Development of TNX-601 ER, a Potential Abuse Deterrent, Extended-Release Formulation of Tianeptine Oxalate for the Treatment of Major Depressive Disorder". Tonix Pharmaceuticals Holding Corp. 11 July 2022. Retrieved 21 October 2024.
- ^ Pergolizzi JV, Raffa RB, Taylor R, Vacalis S (April 2018). "Abuse-deterrent opioids: an update on current approaches and considerations". Curr Med Res Opin. 34 (4): 711–723. doi:10.1080/03007995.2017.1419171. PMID 29262730.
- ^ "Tonix Pharmaceuticals Announces Topline Results from Phase 2 Proof-of-Concept Study of TNX-601 ER for the Treatment of Major Depressive Disorder". BioSpace. 31 October 2023. Retrieved 21 October 2024.