Effects of Aminoadamantane Derivatives on Morphine-Induced Analgesia in Mice

The effects of low-affinity NMDA-receptor antagonists amantadine (1-aminoadamantane hydrochloride) and hemantane [N-(2-adamantyl)hexamethyleneimine hydrochloride] on morphine-induced analgesia in C57Bl/6 mice were studied. Amantadine (10 and 20 mg/kg, i.p.) per se did not affect the latent period of the response in the hot-plate test while hemantane (10 and 20 mg/kg, i.p.) increased dose-dependently pain thresholds 180 and 240 min after administration. Morphine (20 mg/kg, s.c.) showed a time—effect dependence (30 – 120 min). The aminoadamantanes were administered 90 min after the opioid to assess their effects on morphine-induced antinociception. The responses of the animals were recorded for the next 2.5 h. The aminoadamantanes potentiated and extended the analgesic activity of morphine in the order of efficacy amantadine < hemantane. The results indicated that the aminoadamantanes had different capabilities to cause delayed analgesia and modulated opioid antinociceptive activity at the supraspinal level.