Effects of SUN 0588 on various behaviors in experimental models

• Published in: Japanese Journal of Pharmacology Vol. 49; no. suppl; p. 269
• Main Authors: Hirotsu, Ichiro, Nakamura, Shizuo, Horikawa, Yoshiko, Harada, Miyuki, Ishihara, Takafumi
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1989
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)56644-6

SUN 0588, (-)-(1'R, 2'R, 6R)-2-amino-6-(1', 2'-dihydroxypropyl)-5,6,7,8-tetrahydro-4 (3H)-pteridine dihydrochloride, is the cofactor for phenylalanine, tyrosine and tryptophan hydroxylases. First, we investigated its effects on learning and memory in various experimental amnesia models using the step-through passive avoidance task (PA), active avoidance task (AA) or water filled multiple T-maze task (WM); and secondly, we observed its effects on the turning behaviors in mice with a unilateral nigro-striatal lesion by 6-hydroxydopamine. 1) SUN 0588 (3-10 mg/kg, i.p.; 1-3 mg/kg/dayх4, p.o.) significantly inhibited amnesia induced by scopolamine (0.5 mg/kg, s.c.) in mice, while SUN 0588 (0.3-30 μg) given i.cist, was ineffective (PA). 2) SUN 0588 (10 mg/kg, i.p.) inhibited the increase in the number of errors induced by AF64A (1 nmol) injected into the bilateral basal forebrain of rats (WM). 3) SUN 0588 (10 mg/kg, i.p.) improved the impairment of learning in cerebral embolized rats (WM). 4) SUN 0588 (1 mg/kg, i.p.) improved learning deficit in aged rats (AA and WM). 5) SUN 0588 (1 mg/kg, i.p.) caused no turning behavior during a 24 hr observation period, while it produced a slight ipsilateral turning behavior when given i.c.v. at 30 μg. These findings suggest that SUN 0588 may be a promising drug for the treatment of impairment of learning and memory, but that the salutary effect of SUN 0588 may not result from its central action.