In human body, drug‐neurotransmitter interactions have been the most significant process. Whereas, adverse reactions may be accompanied by unexpected interaction, which puts an individual in danger of life. Thus, the interactions between adenosine (ADN) and sodium valproate (SV) with caffeine (CAF), theophylline (TPY) and γ‐amino butyric acid (GABA) have been studied. Various properties like densities, ρ and speed of sound, u, have been used to calculate apparent molar volumes (V2,ϕ) and apparent molar isentropic compression (Ks,2,ϕ) for ADN and SV in aqueous (5, 10, 15 and 20 mmol kg−1) CAF, TPY and GABA solutions at T = (288.15–318.15) K and at pressure p = 1 × 105 Pa. The results of various interactions that occurred by mixing the solutions have been interpreted. Exothermicity is indicated by the negative values of standard molar enthalpy of transfer, ΔtrΔdilH0, obtained from the calorimetry. UV‐absorption and 1H NMR studies suggest that there is a dominance of solute‐cosolute interactions due to hyperchromic shift and shielding effect.