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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1996-11-5
|
| pubmed:abstractText |
N-Oxides of centrally acting analgesics generally have minimal analgesic activity. However, the N-oxide of tramadol produced dose-related, long-lasting antinociception in the mouse abdominal irritant, 48 degrees C hot-plate, 55 degrees C hot-plate, and tail-flick tests (ED50 = 15.5, 84.7, 316.4 and 138.2 mg/kg, p.o., respectively). Tramadol N-oxide (T-N-O) (RWJ 38705) was also antinociceptive in the 51 degrees C hot-plate test in male (ED50 = 63.2 mg/kg, i.p.) and female (ED50 = 39.9 mg/kg, i.p.) rats. A characteristic feature of T-N-O was an extended duration of action in these tests (4-5 h). T-N-O had negligible affinity for opioid mu (Ki = 38.5 microM) delta. or kappa receptors (Ki > 100 microM) and, in contrast to tramadol, was essentially devoid of norepinephrine or serotonin neuronal reuptake inhibitory activity (Ki > 100 microM). However, T-N-O displayed tramadol-like characteristics in vivo. There were also significant amounts of tramadol in plasma after T-N-O administration, and the levels resulting from equal oral doses of T-N-O and tramadol were the same, suggesting that the conversion of T-N-O to tramadol was rapid and essentially quantitative. T-N-O was not readily metabolized to tramadol in rat hepatic S9 fraction (< 2%), implying that the conversion might occur in the gastrointestinal tract. Taken together, the results suggest that T-N-O acts as a prodrug for tramadol. T-N-O could offer the clinical benefits of an extended duration of action and a "blunted" plasma concentration spike, possibly leading to an enhanced side-effect profile.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0022-3565
|
| pubmed:author |
pubmed-author:BubenJ AJA,
pubmed-author:CoddE EEE,
pubmed-author:ConnellyC DCD,
pubmed-author:HaslegoM LML,
pubmed-author:MartinezR PRP,
pubmed-author:MaryanoffC ACA,
pubmed-author:MckownL ALA,
pubmed-author:RaffaR BRB,
pubmed-author:SchupskyJ JJJ,
pubmed-author:TUW CWC,
pubmed-author:TakacsA NAN,
pubmed-author:VillaniF JFJ
|
| pubmed:issnType |
Print
|
| pubmed:volume |
278
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1098-104
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:8819491-Analgesics,
pubmed-meshheading:8819491-Animals,
pubmed-meshheading:8819491-Biological Transport,
pubmed-meshheading:8819491-Dose-Response Relationship, Drug,
pubmed-meshheading:8819491-Female,
pubmed-meshheading:8819491-Liver,
pubmed-meshheading:8819491-Male,
pubmed-meshheading:8819491-Mice,
pubmed-meshheading:8819491-Naloxone,
pubmed-meshheading:8819491-Radioligand Assay,
pubmed-meshheading:8819491-Rats,
pubmed-meshheading:8819491-Rats, Wistar,
pubmed-meshheading:8819491-Receptors, Opioid, mu,
pubmed-meshheading:8819491-Tramadol
|
| pubmed:year |
1996
|
| pubmed:articleTitle |
Unexpected antinociceptive effect of the N-oxide (RWJ 38705) of tramadol hydrochloride.
|
| pubmed:affiliation |
R.W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania, USA.
|
| pubmed:publicationType |
Journal Article
|