Studies on the mechanism of the interaction of narcotic analgesics with brain serotonin

F. Miranda, R. Invernizzi, R. Samanin

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Morphine, pentazocine, methadone and pethidine were tested for their ability to modify serotonin metabolism and the depletion of serotonin induced by fenfluramine in the rat forebrain and brainstem. Their analgesic effect was also studied in animals with electrolytic lesions of the nucleus medianus raphe. Except for a reduction of the effect of fenfluramine on brainstem serotonin by the highest dose of pethidine (30 mg/kg), none of the narcotics examined, unlike chlorimipramine, counteracted the depletion of serotonin induced by fenfluramine in forebrain and brainstem. Increased levels of 5-hydroxy-indoleacetic acid in the forebrain and brainstem were found in animals treated with morphine, whereas pentazocine increased serotonin metabolism only in the forebrain. Of methadone and pethidine only the latter significantly decreased serotonin metabolism in the brainstem. All the compounds examined had less analgesic effect in rats with electrolytic lesions of the nucleus medianus raphe. These findings indicate a complex but significant interaction between the various narcotic analgesics and brain serotonin but are against a relationship between their analgesic activity and their inhibition of serotonin uptake into central neurons.

Original languageEnglish
Pages (from-to)455-466
Number of pages12
JournalPharmacological Research Communications
Volume11
Issue number5
DOIs
Publication statusPublished - 1979

Fingerprint

Narcotics
Serotonin
Brain Stem
Brain
Prosencephalon
Fenfluramine
Meperidine
Pentazocine
Analgesics
Raphe Nuclei
Methadone
Morphine
Clomipramine
Neurons

ASJC Scopus subject areas

  • Pharmacology

Cite this

Studies on the mechanism of the interaction of narcotic analgesics with brain serotonin. / Miranda, F.; Invernizzi, R.; Samanin, R.

In: Pharmacological Research Communications, Vol. 11, No. 5, 1979, p. 455-466.

Research output: Contribution to journalArticle

@article{944ef703ca914d8cbfbcfa33d6d0c1ea,
title = "Studies on the mechanism of the interaction of narcotic analgesics with brain serotonin",
abstract = "Morphine, pentazocine, methadone and pethidine were tested for their ability to modify serotonin metabolism and the depletion of serotonin induced by fenfluramine in the rat forebrain and brainstem. Their analgesic effect was also studied in animals with electrolytic lesions of the nucleus medianus raphe. Except for a reduction of the effect of fenfluramine on brainstem serotonin by the highest dose of pethidine (30 mg/kg), none of the narcotics examined, unlike chlorimipramine, counteracted the depletion of serotonin induced by fenfluramine in forebrain and brainstem. Increased levels of 5-hydroxy-indoleacetic acid in the forebrain and brainstem were found in animals treated with morphine, whereas pentazocine increased serotonin metabolism only in the forebrain. Of methadone and pethidine only the latter significantly decreased serotonin metabolism in the brainstem. All the compounds examined had less analgesic effect in rats with electrolytic lesions of the nucleus medianus raphe. These findings indicate a complex but significant interaction between the various narcotic analgesics and brain serotonin but are against a relationship between their analgesic activity and their inhibition of serotonin uptake into central neurons.",
author = "F. Miranda and R. Invernizzi and R. Samanin",
year = "1979",
doi = "10.1016/S0031-6989(79)80009-0",
language = "English",
volume = "11",
pages = "455--466",
journal = "Pharmacological Research",
issn = "1043-6618",
publisher = "Academic Press",
number = "5",

}

TY - JOUR

T1 - Studies on the mechanism of the interaction of narcotic analgesics with brain serotonin

AU - Miranda, F.

AU - Invernizzi, R.

AU - Samanin, R.

PY - 1979

Y1 - 1979

N2 - Morphine, pentazocine, methadone and pethidine were tested for their ability to modify serotonin metabolism and the depletion of serotonin induced by fenfluramine in the rat forebrain and brainstem. Their analgesic effect was also studied in animals with electrolytic lesions of the nucleus medianus raphe. Except for a reduction of the effect of fenfluramine on brainstem serotonin by the highest dose of pethidine (30 mg/kg), none of the narcotics examined, unlike chlorimipramine, counteracted the depletion of serotonin induced by fenfluramine in forebrain and brainstem. Increased levels of 5-hydroxy-indoleacetic acid in the forebrain and brainstem were found in animals treated with morphine, whereas pentazocine increased serotonin metabolism only in the forebrain. Of methadone and pethidine only the latter significantly decreased serotonin metabolism in the brainstem. All the compounds examined had less analgesic effect in rats with electrolytic lesions of the nucleus medianus raphe. These findings indicate a complex but significant interaction between the various narcotic analgesics and brain serotonin but are against a relationship between their analgesic activity and their inhibition of serotonin uptake into central neurons.

AB - Morphine, pentazocine, methadone and pethidine were tested for their ability to modify serotonin metabolism and the depletion of serotonin induced by fenfluramine in the rat forebrain and brainstem. Their analgesic effect was also studied in animals with electrolytic lesions of the nucleus medianus raphe. Except for a reduction of the effect of fenfluramine on brainstem serotonin by the highest dose of pethidine (30 mg/kg), none of the narcotics examined, unlike chlorimipramine, counteracted the depletion of serotonin induced by fenfluramine in forebrain and brainstem. Increased levels of 5-hydroxy-indoleacetic acid in the forebrain and brainstem were found in animals treated with morphine, whereas pentazocine increased serotonin metabolism only in the forebrain. Of methadone and pethidine only the latter significantly decreased serotonin metabolism in the brainstem. All the compounds examined had less analgesic effect in rats with electrolytic lesions of the nucleus medianus raphe. These findings indicate a complex but significant interaction between the various narcotic analgesics and brain serotonin but are against a relationship between their analgesic activity and their inhibition of serotonin uptake into central neurons.

UR - http://www.scopus.com/inward/record.url?scp=0018761056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018761056&partnerID=8YFLogxK

U2 - 10.1016/S0031-6989(79)80009-0

DO - 10.1016/S0031-6989(79)80009-0

M3 - Article

C2 - 39300

AN - SCOPUS:0018761056

VL - 11

SP - 455

EP - 466

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

IS - 5

ER -