Potentiation of the locomotor activity of memantine by aminophylline

1-Amino-3,5-dimethyladamantane hydrochloride (memantine, D-145, Akatinol) and aminophylline were shown to increase the locomotor activity of mice in a dose-dependent manner; yet the effect of aminophylline took place and decreased faster than that of memantine. The ED25 for memantine was found to be 4 mg/kg; the moderate increase of locomotor activity caused by this dose of memantine was potentiated by aminophylline. The combination of both led to an over-additive immediate onset of effect and was longer lasting than that produced by memantine alone. An optimal potentiation of memantine effect was reached when it was combined with aminophylline in molar ratio of 1:2. The possible mechanism of this synergistic effect is discussed.