TRV250

TRV250 is a δ-opioid receptor (DOR) agonist which is under development for the treatment of migraine.^[1]^[3]^[2]^[4] It is taken orally.^[1]^[2] The drug shows high selectivity for the DOR over the μ- and κ-opioid receptors.^[4] It is a biased agonist of the DOR, with preference for activation of G protein signaling over β-arrestin2 signaling.^[2] TRV250 produces analgesic, antimigraine-like, antidepressant-like, and anxiolytic-like effects in rodents.^[2] In addition, it has dramatically reduced proconvulsant activity relative to non-biased DOR agonists in rodents and monkeys, with a 50- to 80-fold margin between analgesia and seizures.^[2] TRV250 is being developed by Trevena.^[1]^[3] As of April 2025, the drug is in phase 2 clinical trials for treatment of migraine.^[1]^[3] No recent development has been reported for treatment of CNS disorders, while development for treatment of neuropathic pain and Parkinson's disease was discontinued.^[1]^[3] TRV250 was first described in the scientific literature in 2015.^[4]

Other namesTRV-250

Routes of
administrationOral^[1]^[2]

Drug classδ-Opioid receptor agonist; Analgesic; Antimigraine agent

Bioavailability14–19% (relative to s.c.)^[2]

Quick facts Clinical data, Other names ...

TRV250
Clinical data
Other names	TRV-250
Routes of administration	Oral^[1]^[2]
Drug class	δ-Opioid receptor agonist; Analgesic; Antimigraine agent
Pharmacokinetic data
Bioavailability	14–19% (relative to s.c.Tooltip subcutaneous injection)^[2]
Elimination half-life	2.4–3.8 hours^[2]

References

[1]
"TRV 250". AdisInsight. 28 April 2025. Retrieved 9 January 2026.
[2]
Fossler MJ, Schmith V, Greene SA, Lohmer L, Kramer MS, Arscott K, et al. (August 2020). "A Phase I, Randomized, Single‑Blind, Placebo‑Controlled, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneous and Oral TRV250, a G Protein-Selective Delta Receptor Agonist, in Healthy Subjects". CNS Drugs. 34 (8): 853–865. doi:10.1007/s40263-020-00738-0. PMC 7392943. PMID 32676977. TRV250 is a novel small molecule agonist of the DOR that acts in a manner preferentially selective for G-protein signaling, with relatively little activation of the β-arrestin2 post-receptor signaling pathway. Findings from nonclinical studies have shown a substantial reduction in proconvulsant activity with TRV250 compared with other, non G-protein selective DOR agonists, with an established 50- to 80-fold margin between therapeutic effect and seizures in rodents and monkeys (Data on File). In the nitroglycerin-evoked hyperalgesia model in rodents used to screen candidates for potential utility in acute migraine [16], TRV250 significantly reduced hyperalgesia (Data on File). [...] Peak and total plasma exposure to TRV250 increased in a dose-proportional manner following 0.1–30 mg SC doses, with the mean half-life ranging from 2.39 to 3.76 h. Oral bioavailability of TRV250 was acceptable and ranged from 14% (fasting) to 19% (fed) relative to SC dosing.
[3]
"Delving into the Latest Updates on TRV-250 with Synapse". Synapse. 3 January 2026. Retrieved 9 January 2026.
[4]
Crombie AL, Arezzo J, Cowan CL, DeWire SM, Gowen-MacDonald W, Hawkins MJ, et al. (November 2015). "TRV250: a novel biased ligand at the delta receptor for the potential treatment of migraine: lbp17". Headache. 55: 264–265. doi:10.1111/head.12693. PMID 26422810. RESULTS: Compared to unbiased agonists AZD2327 and SNC80, TRV250 has potent, full efficacy for G protein coupling, but much weaker engagement of beta-arrestin2. TRV250 is highly selective for the DOR over the mu and kappa opioid receptors. In rodent nitroglycerin-induced hyperalgesia models of migraine, TRV250 showed robust efficacy after both subcutaneous and oral dosing. TRV250 was also active in models of nociception, depression, and anxiety. Compared to AZD2327, TRV250 showed a markedly improved margin between efficacious doses and doses associated with seizure.

See also

References

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