Modification of morphine analgesia by drugs affecting adrenergic and tryptaminergic mechanisms

Abstract

The effects of drugs that modify adrenergic or tryptaminergic mechanisms were tested on the analgesic action of morphine in mice. Analgesia was assessed by the hot plate method and phenylquinonewrithing method. Reserpine antagonized the analgesic action of morphine in both tests, the maximal effects occurring 6–8 h after the administration of reserpine. p‐Chlorophenylalanine antagonized the analgesic action of morphine as assessed by the writhing method but not by the hot plate method. The analgesic action of morphine was not modified in either test by pretreatment with α‐methyl‐p‐tyrosine, propranolol, phentolamine or methysergide. These results suggest that the analgesic action of morphine, as measured in the writhing test, may be mediated by 5‐hydroxytryptamine but that other mechanisms may be involved in the hot plate test.

5‐HT‐Uptake Inhibition Potentiates Antinociception Induced by Morphine, Pethidine, Methadone and Ketobemidone in Rats

“…1980;Larsen & Christensen 1982;Larsen & Arnt 1984). In accordance, a reduction of morphineinduced antinociception is obtained following destruction of 5-HT neurones by 5, 7 -dihydroxytryptamine (5,7-DHT), following 5-HT-synthesis inhibtion by para-chlorophenylalanine (PCPA), or following receptor blockade by 5-HT-receptor antagonists (Fennessy & Lee 1970;Yaksh eta/. 1976;Mohrland & Gebhart 1980).…”

Effects of α‐methyl‐p‐tyrosine, p‐chlorophenylalanine, l‐β‐(3,4‐dihydroxyphenyl)alanine, 5‐hydroxytryptophan and diethyldithiocarbamate on the analgesic activity of morphine and methylamphetamine in the mouse

“…A similar conclusion was reached by Colville & Chaplin (1964) using the rat inflamed foot as the analgesic testing method. Diminution of the analgesic activity of morphine by propranolol has been reported in the mouse (Heller, Saavedra & Fischer, 1968), but Fennessy & Lee (1970) were unable to confirm this observation.…”

“…A similar conclusion was reached by Colville & Chaplin (1964) using the rat inflamed foot as the analgesic testing method. Diminution of the analgesic activity of morphine by propranolol has been reported in the mouse (Heller, Saavedra & Fischer, 1968), but Fennessy & Lee (1970) (Collins & West, 1968) and although its actions in the brain are more complicated, Carlsson, Lindqvist, Fuxe & Hokfelt (1966) demonstrated a general fall in brain noradrenaline and a rise in dopamine in the brain stems and hemispheres of the rat. Increases in reaction time were obtained with mice pretreated with a-methyl-p-tyrosine in the presence of morphine and methylamphetamine.…”

“…a-Methyl-m-tyrosine decreases (Medakovic & Banic, 1964) and has no effect on (Rudzik & Mennear, 1965) morphine analgesia in the mouse. Similarly a-methyl-ptyrosine decreases (Verri, Graeff & Corrado, 1967) and has no effect on (Fennessy & Lee, 1970) morphine analgesia. Depletion of brain 5-HT using p-chlorophenylalanine abolishes (Tenen, 1968) or has no effect on (Fennessy & Lee, 1970) morphine analgesia.…”

“…Similarly a-methyl-ptyrosine decreases (Verri, Graeff & Corrado, 1967) and has no effect on (Fennessy & Lee, 1970) morphine analgesia. Depletion of brain 5-HT using p-chlorophenylalanine abolishes (Tenen, 1968) or has no effect on (Fennessy & Lee, 1970) morphine analgesia. However, both 5-HT and 5-hydroxytryptophan enhance the analgesia produced by morphine (Sigg et al, 1958;Mercier, Etzensperger & Mercier, 1959).…”