Cyclic adenosine monophosphate antagonism of morphine analgesia

I. K. Ho, H. H. Loh, E. L. Way

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

The administration of cyclic adenosine 3',5' monophosphate (cAMP) intracerebrally or intravenously antagonized morphine analgesia in nontolerant and tolerant mice. The cAMP surrogates dibutyryl cAMP, a phosphodiesterase resistant cAMP analog, and theophylline, a phosphodiesterase inhibitor, acted in a similar manner. The antagonism of morphine effects by all three compounds persisted for at least 24 hr and may have lasted for 48 hr. Elevation of brain biogenic amines by monoamine oxidase inhibition with pargyline reversed the antagonistic effects of cAMP on morphine analgesia. Increasing brain dopamine with L dopa did not prevent cAMP antagonism of morphine analgesia. Increasing brain serotonin with tryptophan not only failed to reverse the effect of cAMP, but also appeared to enhance the cAMP response. However, elevation of norepinephrine with dihydroxyphenylserine did reverse the antagonistic effect of cAMP. It is included, therefore, that norepinephrine is more important for the reversal of cAMP antagonism of morphine analgesia than either dopamine or serotonin.

Original languageEnglish (US)
Pages (from-to)336-346
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume185
Issue number2
StatePublished - Dec 1 1973

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Cyclic AMP
Analgesia
Morphine
Dopamine
Serotonin
Norepinephrine
Biogenic Monoamines
Brain
Pargyline
Bucladesine
Biogenic Amines
Phosphodiesterase Inhibitors
Monoamine Oxidase
Phosphoric Diester Hydrolases
Levodopa
Theophylline
Tryptophan

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Cyclic adenosine monophosphate antagonism of morphine analgesia. / Ho, I. K.; Loh, H. H.; Way, E. L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 185, No. 2, 01.12.1973, p. 336-346.

Research output: Contribution to journalArticle

Ho, I. K. ; Loh, H. H. ; Way, E. L. / Cyclic adenosine monophosphate antagonism of morphine analgesia. In: Journal of Pharmacology and Experimental Therapeutics. 1973 ; Vol. 185, No. 2. pp. 336-346.
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