ABSTRACT
Aim To investigate the inhibitory effects of the novel compounds YZG-330 and YZG-331 in central nervous system. Methods The sedative effect was investigated by recording the spontaneous locomotor ac-tivity in mice. The hypnotic effect was evaluated by the latency and duration of the loss of righting reflex ( LORR) in the threshold dosage of sodium pentobarbi-tal treated mice. The two compounds induced the mice that had woken up after a threshold dosage pentobarbi-tal sodium to fall asleep again. The levels of GABA and Glu in brain were measured by HPLC-ECD. Re-sults The results showed that spontaneous locomotor activities decreased in YZG-330 (0.125, 0.5,2 mg·kg-1 ) treated mice and YZG-331 (1.25, 5, 20 mg· kg-1 ) treated mice. YZGs could extend the duration of the loss of righting reflex in threshold dosage of sodium pentobarbital treated mice, and significantly shorten sleep latency. YZGs were able to allow the mice that had woken up after a threshold dosage pentobarbital so-dium to fall asleep again. YZG-331 (40 mg·kg-1 ,i. g. ) could significantly increase GABA level in hypo-thalamus and cerebral cortex. The content of GABA had no significant change after YZG-330 ( 2 mg · kg-1 , ig. ) administration. Conclusions YZG-330 and YZG-331 have potent sedative and hypnotic effects. The efficacy of YZG-330 is stronger than that of YZG-331 , but the mechanism of two compounds sounds different.
ABSTRACT
Adenosine receptors (AR) play an important role in the regulation processes for body temperature and vigilance states. During our previous studies, we noticed that aminophylline (a non-selective, blood-brain-barrier penetrably AR antagonist) could attenuate the effects of YZG-330 [(2R,3S,4R,5R)-2-(hydroxymethyl-5-(6-(((R)-1-phenylpropyl)amino)-9H-purin-9-yl)tetrahydrofuran-3, 4-diol] on lowering the body temperature. Hereby, we focused ourselves on the character of thermal regulation effect of YZG-330 in mice and tried to specify the receptor subtype via giving typical adenosine receptor antagonists. The results showed that both of the magnitude and lasting time of the effect that YZG-330 played on decreasing body temperature are in a dose-dependent manner: within the next 3 hour after intragastric administration (ig) of 0.25, 1 or 4 mg . kg-1 YZG-330, the extreme values on body temperature decreasing were (1.2 ± 0.3) °C, (3.6 ± 0.4) °C (P<0.001) and (7.4±0.5) °C (P<0.001), separately; whereas the duration that body temperature below 34 °C were 0, (10±5) and (153±4) min, separately. Adenosine A1 receptor (A1R) antagonist (DPCPX) could effectively reverse YZG-330's effect on decreasing body temperature, with intraperitoneal administration of DPCPX (5 mg . kg-1) 20 min prior than YZG-330 (4 mg.kg-1, ig), the extreme value on body temperature decreasing was (3.5 ± 0.7) °C (P<0.001), the duration that body temperature below 34 °C was (8±6) min (P<0.001). However, adenosine A2a receptor antagonist, SCH-58261, did not show any influence on the effects of YZG-330 at all. Combined with the fact that 8-SPT (a non-selective, blood-brain-barrier impenetrably AR antagonist) did not reverse the effect of YZG-330, we come to the conclusion that central-adenosine A, receptor plays a significant role on the thermal regulation effect of YZG-330.