Neurochemical and behavioral studies on the mode of action of oxypertine

The mode of action of 1-[2-(5,6-dimethoxy-2-methyl-3-indole) ethyl]-4-phenylpiperidine (oxypertine) was re-examined neurochemically and behaviorally. The results obtained in the present study differed from those reported to date in the following respects. Oxypertine caused an obvious dose-related depletion in the levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in various discrete regions of the rat brain. The depletion in NE and DA levels were more remarkable than that in 5-HT levels. A uniform, but not statistically significant decrease in the NE level occurred throughout the rat brain at a dose level of 10 mg/kg i.p. However, the same dose of oxypertine caused significant reduction of the DA levels in the cortex and striatum. The level of homovanillic acid in three discrete regions, i.e., the cortex, striatum and mid-brain, increased in a dose-dependent manner following oxypertine administration. However, there was no difference in the level of 3,4-dihydroxyphenylacetic acid (DOPAC) at the two different dosages examined, i.e., 10 and 35 mg/kg i.p., although DOPAC levels increased significantly. Pretreatment with oxypertine at relatively smaller dosages than mentioned above inhibited apomorphine-induced stereotypy in a dose-dependent manner. Thus, it seems reasonable to conclude that at dose levels within the therapeutic range oxypertine affects mainly the dopaminergic mechanism, but it also affects the noradrenergic mechanism and thereby achieves its favorable antipsychotic action on schizophrenia.