Abstract
Spinal blockade of 5-HT7 receptors has been reported to inhibit the antinociceptive effect of opioids. In this study, we found that subcutaneous administration of the selective 5-HT7 receptor agonist E-55888 (10 mg/kg) or the antagonist SB-258719 (5 mg/kg) exerted no effect on the tail-flick test in mice. However, E-55888, but not SB-258719, increased (2.6-fold) the analgesic potency of oral morphine. The potentiating effect exerted by E-55888 was prevented by SB-258719. A pharmacokinetic interaction was discarded as morphine plasma and brain concentrations were not significantly modified when co-administered with E-55888. These results reinforce the involvement of 5-HT7 receptors in opioid analgesia and point to a potential use of 5-HT7 receptor agonists as adjuvants of opioid analgesia.
MeSH terms
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Analgesia / methods
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Analgesics, Opioid / pharmacokinetics
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Analgesics, Opioid / pharmacology*
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Animals
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Drug Synergism
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Male
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Mice
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Morphine / blood
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Morphine / pharmacokinetics
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Morphine / pharmacology*
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Pain / drug therapy*
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Pain / metabolism
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Pain Measurement / drug effects
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Piperidines / pharmacology
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Pyrazoles / pharmacokinetics
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Pyrazoles / pharmacology*
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Receptors, Serotonin / metabolism*
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / pharmacology*
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Sulfonamides / pharmacology
Substances
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3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide
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Analgesics, Opioid
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Piperidines
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Pyrazoles
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Receptors, Serotonin
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Sulfonamides
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dimethyl-(2-(3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)ethyl)amine dihydrochloride
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serotonin 7 receptor
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Morphine