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СпутникиРНSpaceXРоскосмосNASARelevance. The search for a potent and safe analgesic devoid of the disadvantages of opioids and non steroidal anti inflammatory drugs remains an unresolved challenge in pharmacology. The synthetic isoquinoline derivative 6 (3,3 dimethyl 3,4 dihydroisoquinolin 1 yl)aminohexanoic acid (G-104) has demonstrated marked analgesic activity in preclinical models; however, its molecular targets and mechanism of action have remained unidentified.Objective. To predict the potential peripheral targets 5-HTЗА and DP2 and analgesic mechanism of this novel isoquinoline derivative using a comprehensive in silico analysis.Methods. Target prediction (SwissTargetPrediction, SEA, TargetNet, PPB2), molecular docking (Glide), and molecular dynamics simulations (GROMACS) were performed.Results. In combination with previously obtained experimental data, a hypothesis on the possible mechanism of G-104 analgesia is proposed. The serotonin 5-HT ЗА receptor and the prostaglandin DP₂ receptor were selected as potential targets. Docking revealed that G-104 forms complexes with both receptors characteristic of antagonists, and molecular dynamics for DP₂ confirmed the stability of the binding pose throughout the simulation trajectory. This dual peripheral mechanism—simultaneous inhibition of serotonergic pain modulation and pro inflammatory prostaglandin D₂ signaling—may be consistent with potent and prolonged analgesia observed in vivo and predicts a low risk of central and autonomic adverse effects.Conclusion. The obtained results position G-104 as a potentially effective multitarget analgesic and pave the way for further preclinical investigations.
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