Potentiation by nitric oxide synthase inhibitor and calcium channel blocker of aspartame-induced antinociception in the mouse formalin test.
By applying a 12 day regimen of the non-calorific sweetener, aspartame, in combination with representative compounds of the calcium channel blocker and nitric oxide synthase inhibitor, we tried to investigate using a formalin-test in mice the relative role of aspartame on pain and its mechanism of action. Verapamil (2, 3.5, 5, 7.5 mg/kg) induced significant (P < 0.01) antinociception in both phases of the formalin test. L-Nitro-arginine-methyl-ester (L-NAME) at the doses used, induced significant (P < 0.01) antinociception in early phase (1, 2, 5, 10 mg/kg) and late phase (5, 10 mg/kg). Twelve days of treatment in animals by aspartame (0.16% w/v) significantly induced antinociception in both phases of the formalin test. Both verapamil (5 mg/kg) and L-NAME (10 mg/kg) significantly (P < 0.01) potentiated aspartame-induced antinociception in both phases of formalin test. The present findings support the hypothesis that the activation of NMDA receptors by aspartame modulates pain-related behaviour via a nitric oxide/cGMP/glutamate release cascade. It is concluded that aspartame would be a good analgesic agent if it would be used in combination with a calcium channel blocker or NOS inhibitor.
Abdollahi
M
M
Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14155-6451, Iran. mabdol@yahoo.com
Nikfar
S
S
Abdoli
N
N
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001218:Aspartame / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D000700:Analgesics; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D014700:Verapamil; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D001218:Aspartame