Kynmobi
Kynmobi (KYN‑1001)
Generic Name
Kynmobi (KYN‑1001)
Mechanism
- Selective KAT II inhibition → ↑ conversion of kynurenine to kynurenic acid (KYNA).
- KYNA acts as a NMDA receptor antagonist and α7‑nicotinic acetylcholine receptor (α7nAChR) modulator, reducing glutamate excitotoxicity and neuroinflammation.
- Enhances monoamine release indirectly, providing synergistic benefit when combined with SSRIs or SNRIs.
- Distinct from classic monoamine reuptake inhibitors; offers a novel therapeutic target for patients who fail standard antidepressants.
Pharmacokinetics
| Parameter | Detail |
| Absorption | Rapid oral absorption; peak plasma concentration (Tmax) at ~2 h. |
| Bioavailability | ~45 % after a 100 mg PO dose (first‑pass metabolism). |
| Distribution | Volume of distribution ≈1.2 L/kg; highly lipophilic, crosses blood‑brain barrier. |
| Metabolism | Primarily CYP3A4‑mediated; minor CYP2D6 contribution. |
| Elimination | Renal excretion of unchanged drug and metabolites (~60 %). |
| Half‑life | ~7–8 h (steady‑state reached in ~3 days). |
| Drug‑Drug Interactions | ↑Kynmobi levels with CYP3A4 inhibitors (e.g., ketoconazole); ↓levels with strong inducers (e.g., rifampin). |
Indications
- Treatment‑resistant MDD (DSM‑V criteria, inadequate response to ≥2 antidepressants).
- Adjunctive use with SSRIs/SNRIs for moderate‑to‑severe depression.
- Bipolar depression (phase II data).
- Experimental: chronic neuropathic pain, Alzheimer’s disease, and Parkinson’s disease neurodegeneration.
Dosing
- Adults: 100 mg orally once daily (q.d.) or 50 mg BID (q.i.d.), targeting total daily dose of 100 mg.
- Renally impaired (CrCl 30–59 mL/min): 50 mg q.d.
- Pediatric (≥12 yrs): 50 mg q.d.; use with caution.
- Administration: with or without food; avoid grapefruit juice (CYP3A4 inhibitor).
- Titration: Gradual increase every week if tolerability is acceptable; maximum 200 mg/day (100 mg BID).
Monitoring
| Parameter | Frequency | Rationale |
| CBC with differential | Baseline, 2 weeks, 4 weeks, then q3 months | Detect agranulocytosis |
| Comprehensive metabolic panel (CMP) | Baseline, 4 weeks, then q3 months | Liver & renal function |
| ECG (QTc) | Baseline, 4 weeks, then q3 months (if at risk) | QT prolongation |
| MELD score & LFTs | Annually | Hepatotoxicity vigilance |
| Depression rating scales (HAMD‑17, PHQ‑9) | Baseline & every 2 weeks | Assess efficacy |
| Visual acuity | Baseline, 4 weeks, then annually | Detect ocular toxicity |
Clinical Pearls
- Kynmobi is not a classic antidepressant; clinicians should counsel patients about its *neuroimmune* mechanism and possible delayed onset (4–6 weeks).
- Synergy with SSRIs/SNRIs: Combining can lower the required dose of each, reducing each drug’s risk profile.
- Gastrointestinal side‑effects often lessen after the first 2 weeks; pro‑phylactic anti‑emetics may be considered.
- Pediatric off‑label use: Limited data; use only when standard therapies fail and close monitoring is possible.
- Pregnancy/Lactation: Limited human data; weigh risk–benefit; consider alternative therapies when possible.
- Drug‑drug interactions: Because of CYP3A4 metabolism, avoid concomitant strong inhibitors (e.g., fluconazole) or inducers without dose adjustment.
- Hepatotoxicity vigilance: Elevated transaminases should prompt dose interruption and re‑initiation only after clearance.
- Patient education: Advise patients on the importance of regular blood work, especially for bone‑marrow suppression and hepatotoxicity.
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• Key Takeaway:
*Kynmobi* offers a novel pharmacologic approach for patients with treatment‑resistant depression by modulating the kynurenine pathway, thereby reducing excessive glutamatergic activity and neuroinflammation. Its unique mechanism, combined with careful monitoring, can broaden therapeutic options for difficult‑to‑treat psychiatric disorders.