Time course for effects of sulpiride and chlorpromazine on monoamine metabolite and prolactin levels in cerebrospinal fluid from schizophrenic patients.
Schizophrenic patients were treated with the dopamine (DA)-2 receptor blocking drug sulpiride (800 mg daily) or the non-selective DA receptor blocking compound chlorpromazine (400 mg daily). Samples of lumbar cerebrospinal fluid (CSF) and blood were drawn before and after 1, 2, 4 and 8 weeks of treatment. Concentrations of the monoamine metabolites HVA, MOPEG and 5-HIAA in CSF and of prolactin (PRL) in CSF and serum were determined. In both treatment groups there were significant and similar elevations of HVA concentrations. HVA levels reached peaks after 1 to 2 weeks treatment and subsequently declined almost to the pretreatment level after 8 weeks. CSF and serum levels of PRL reached maximal levels within 2 weeks and remained stable at that level in both treatment groups. There were significantly higher PRL levels in sulpiride- than in chlorpromazine-treated patients. Women had higher PRL elevations in CSF in both treatment groups. The HVA/PRL ratio in CSF was significantly reduced in the sulpiride but not in the chlorpromazine group. After 1 week there was a significantly elevated 5-HIAA level in the chlorpromazine but not in the sulpiride group. In both groups, the MOPEG concentrations were significantly reduced in relation to pretreatment levels. The reduction was significantly more pronounced in the chlorpromazine group. The results indicate that sulpiride affects central DA metabolism in a similar way as chlorpromazine when administered in doses that induce antipsychotic effects. After both drugs evidence was obtained for the development of tolerance to the effect on the receptors that regulate HVA levels in the CSF but not to receptors regulating PRL release. The different effects of the drugs on PRL, 5-HIAA and MOPEG levels indicate that sulpiride has a more specific effect than chlorpromazine on dopaminergic mechanisms.
D000293:Adolescent; D000328:Adult; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis; D002746:Chlorpromazine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D011388:Prolactin / Q000134:cerebrospinal fluid*; D017448:Receptors, Dopamine D2; D012559:Schizophrenia / Q000188:drug therapy*; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
D002556:Cerebrospinal Fluid Proteins; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D013469:Sulpiride; D011388:Prolactin; D002746:Chlorpromazine; D006719:Homovanillic Acid