Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice

H. F. Miranda, M. M. Puig, M. A. Romero, J. C. Prieto

Resultado de la investigación: Article

21 Citas (Scopus)

Resumen

The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo-oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re-uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed-dose method GIT. The administration of DEX or TRAM individually induced dose-dependent antinociception in all the algesiometric tests. In the three tests, TRAM was between 5.2 (FT, phase I) and 35 times (FT, Phase II) more potent than DEX. When testing combinations at different potency ratios (1 : 1, 1 : 3, 3 : 1), we could demonstrate synergy in all algesiometric tests, only when drugs were combined in a 1 : 1 proportion. Interestingly, the proportion of the drugs in the combination could change the type of interaction from synergy to antagonism. On the inhibition of GIT, a dose-related inhibition was established for TRAM, but not for DEX. Using a fixed-dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans.

Idioma originalEnglish
Páginas (desde-hasta)81-88
Número de páginas8
PublicaciónFundamental and Clinical Pharmacology
Volumen23
N.º1
DOI
EstadoPublished - feb 2009

Huella dactilar

Gastrointestinal Transit
Tramadol
Analgesia
Cyclooxygenase Inhibitors
Charcoal
Drug Combinations
Pain Measurement
Acetic Acid
Opioid Analgesics
Meals
Tail
Serotonin
Norepinephrine
Clinical Trials
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Citar esto

Miranda, H. F. ; Puig, M. M. ; Romero, M. A. ; Prieto, J. C. / Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice. En: Fundamental and Clinical Pharmacology. 2009 ; Vol. 23, N.º 1. pp. 81-88.
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Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice. / Miranda, H. F.; Puig, M. M.; Romero, M. A.; Prieto, J. C.

En: Fundamental and Clinical Pharmacology, Vol. 23, N.º 1, 02.2009, p. 81-88.

Resultado de la investigación: Article

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T1 - Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice

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AU - Puig, M. M.

AU - Romero, M. A.

AU - Prieto, J. C.

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N2 - The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo-oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re-uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed-dose method GIT. The administration of DEX or TRAM individually induced dose-dependent antinociception in all the algesiometric tests. In the three tests, TRAM was between 5.2 (FT, phase I) and 35 times (FT, Phase II) more potent than DEX. When testing combinations at different potency ratios (1 : 1, 1 : 3, 3 : 1), we could demonstrate synergy in all algesiometric tests, only when drugs were combined in a 1 : 1 proportion. Interestingly, the proportion of the drugs in the combination could change the type of interaction from synergy to antagonism. On the inhibition of GIT, a dose-related inhibition was established for TRAM, but not for DEX. Using a fixed-dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans.

AB - The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo-oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re-uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed-dose method GIT. The administration of DEX or TRAM individually induced dose-dependent antinociception in all the algesiometric tests. In the three tests, TRAM was between 5.2 (FT, phase I) and 35 times (FT, Phase II) more potent than DEX. When testing combinations at different potency ratios (1 : 1, 1 : 3, 3 : 1), we could demonstrate synergy in all algesiometric tests, only when drugs were combined in a 1 : 1 proportion. Interestingly, the proportion of the drugs in the combination could change the type of interaction from synergy to antagonism. On the inhibition of GIT, a dose-related inhibition was established for TRAM, but not for DEX. Using a fixed-dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans.

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KW - Gastrointestinal transit

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JO - Fundamental and Clinical Pharmacology

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