Effect alteration of methamphetamine by amino acids or their salts on ambulatory activity in mice

Effect alterations of methamphetamine by pretreatment of amino acids or their salts on ambulatory activity in mice were investigated to confirm a fact that certain amino acids, particularly monosodium L-glutamate, are added to methamphetamine by the street users, and that the amino acids augment the effect of methamphetamine. The ambulatory activity of mouse was measured by a tilting-type round activity cage of 25 cm in diameter. The amino acids or their salts tested were monosodium L-glutamate, monosodium L-aspartate, gamma-amino-butyric acid, L-alanine, L-lysine hydrochloride and L-arginine hydrochloride. A single administration of each chemical at doses of 1 and 2 g/kg i.p. did not induce a marked change in the ambulatory activity in mice. Methamphetamine 2 mg/kg s.c. induced an increase in the ambulatory activity with a peak at 40 min after the administration, and the increased ambulatory activity persisted for 3 hr. The ambulation-increasing effect of methamphetamine was augmented by the pretreatment of monosodium L-glutamate and monosodium L-aspartate at 30 min before the methamphetamine administration, while attenuated by the pretreatment of L-lysine hydrochloride and L-arginine hydrochloride in a dose-dependent manner. Gamma-aminobutyric acid and L-alanine did not affect the effect of methamphetamine. Similar augmentation and attenuation in the ambulation-increasing effect of methamphetamine were induced by the pretreatment of sodium bicarbonate 0.9 g/kg i.p. (urinary alkalizer) and ammonium chloride 0.07 g/kg i.p. (urinary acidifier), respectively. The urinary pH level was elevated by the administration of monosodium L-glutamate, monosodium L-aspartate and sodium bicarbonate, and decreased by L-lysine hydrochloride, L-arginine hydrochloride and ammonium chloride. Gamma-aminobutyric acid and L-alanine did not elicit a marked change in the urinary pH level. The present experiment confirms the fact in human that monosodium L-glutamate augments the effect of methamphetamine. Moreover, the present results suggest that monosodium salts of acidic amino acids augment, and conversely monohydrochloric salts of basic amino acids attenuate the effect of methamphetamine. The alterations of the ambulation-increasing effect of methamphetamine may be due to the urinary excretion rates of the drug through changes in the urinary pH level after the administration of amino acids or their salts.