Treatment with para-chlorophenylalanine antagonises the emetic response and the serotonin-releasing actions of cisplatin in cancer patients.
To test the role of serotonin in chemotherapy-induced nausea and emesis, ten cancer patients were pretreated with the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA). PCPA (2 g 8 hourly for 2 or 3 days prior to cisplatin) reduced the spontaneous urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), inhibited the increase in urinary 5-HIAA induced by cisplatin and markedly attenuated the acute period of nausea and vomiting associated with the cytotoxic drug. These results indicate that gastrointestinal serotonin mediates cisplatin-induced emesis and that the amount of serotonin released by cisplatin is a major factor in determining the severity of the acute period of emesis experienced by the patient.
Alfieri
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Department of Pharmacology, School of Pharmacy, Central University of Venezuela.
Cubeddu
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LX
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D005260:Female; D010134:Fenclonine / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000652:urine; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000652:urine; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D007262:Infusions, Intravenous; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control / Q000652:urine; D012701:Serotonin / Q000378:metabolism*; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control* / Q000652:urine
D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002945:Cisplatin; D010134:Fenclonine