In silico investigation of ketamine and methylphenidate drug-drug conjugate for MDD and ADHD treatment using MD simulations and MMGBSA
Scientific Reports July 8, 2025 Beenish Asrar, Nouman Ali, Imran Ali et al.
A computer-designed conjugate of ketamine and methylphenidate shows promise as a potential drug for both major depressive disorder and attention-deficit hyperactivity disorder. The conjugate was designed in ChemDraw and evaluated using computational tools for drug-likeness, toxicity, and binding to the target protein tryptophan hydroxylase 2 (TPH2). Molecular docking revealed the conjugate had a stronger binding affinity (−8.5 Kcal/mol) to TPH2 compared to ketamine alone (−6.7 Kcal/mol) or methylphenidate alone (−6.9 Kcal/mol). The conjugate was predicted to cross the blood-brain barrier, be non-toxic, and form stable interactions with TPH2, suggesting it is a safe candidate for enzyme-based therapeutics.