Small Molecule · MK-1942

MK-1942

DiscontinuedMerck & Co., Inc. (MRK)

Investigational selective negative allosteric modulator of metabotropic glutamate receptor 2 (mGluR2/GRM2), from Merck (MSD). By blocking the presynaptic mGluR2 autoreceptor it increases glutamate cycling (a ketamine-like rapid-antidepressant rationale). Studied as adjunctive therapy in treatment-resistant depression; the program was voluntarily terminated in 2023.

Also known as: MK-1942

Data current as of

Modality
Small molecule
Mechanism
mGluR2 NAM
Highest phase
Discontinued
Lead indication
Treatment-resistant depression
Developer
Merck & Co., Inc. (MRK)
Trials
1 tracked · 45 sites

Mechanism of action

Negative allosteric modulator of mGluR2 (GRM2); relieving mGluR2 autoreceptor restraint increases glutamate release/cycling (MRS-confirmed in non-human primates) — postulated to drive rapid, ketamine-like antidepressant effects. NOT a muscarinic M1 PAM.

TargetActionAffinity
mGluR2primaryGRM2NAM—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
MK-1942 oral (twice-daily, titrated)
Oral capsules; total daily dose titrated 5 mg (Week 1) to 20 mg BID over 4 weeks in the Phase 2 TRD study
OralTwice daily—
MK-1942 oral (twice-weekly, intermittent)
Oral capsules; 10 mg twice weekly (intermittent-dose arm) in the Phase 2 TRD study
OralTwice weekly—

Development timeline

DiscontinuedSept 2023
  1. Program voluntarily terminated after asymptomatic LFT elevations; no significant MADRS difference vs placebo.↗
Phase 2May 2021
  1. Phase 2a TRD trial (MK-1942-006, NCT04663321) initiated, added to stable antidepressant therapy.

MK-1942 for Treatment-resistant depression

DiscontinuedDiscontinuedTreatment-resistant depression indication →

Phase 2a (MK-1942-006 / NCT04663321) as adjunctive therapy in treatment-resistant depression. Voluntarily terminated in 2023 on benefit/risk after asymptomatic liver-function-test elevations; no significant MADRS efficacy vs placebo for either dosing regimen.

Clinical trials

NCT04663321MK-1942-006Phase 2Discontinuedn=99

Phase 2a Study of MK-1942 Added to Stable Antidepressant Therapy in Treatment-Resistant Depression

Started May 2021· Primary completion Sept 2023· 📍 45 sites across 1 country (United States)

missedprimaryMADRS change from baseline

No significant efficacy difference vs placebo for either daily or twice-weekly dosing; study terminated early for asymptomatic LFT elevations.

Related compounds

More from Merck & Co., Inc.

Identifiers

    Sources

    1. Efficacy and Safety of MK-1942 When Added to Stable Antidepressant Therapy in Participants With Treatment-Resistant Depression (TRD) (MK-1942-006) — ClinicalTrials.gov
    2. MSD terminates Phase II trials (liver toxicity) — Clinical Trials Arena
    3. Phase 2 Clinical Trial of MK-1942, an mGluR2 NAM, for TRD — J Clinical Psychopharmacology