Arch Pharm (Weinheim). 1999 Jun;332(6):208-12.
Synthesis and analgesic activity of some condensed analogs of anpirtoline.

Radl S, Kovarova L, Hezky P, Vosatka V, Konigova O, Proska J, Krejci I.

Research Institute of Pharmacy and Biochemistry, Prague, Czech Republic.

New condensed derivatives of anpirtoline, in which the pyridine ring is replaced with quinoline, isoquinoline, quinazoline, and phthalazine nuclei, have been synthesized. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. The analgesic activity of compounds 7d, 8b, 8c, and 8e are at least comparable to that of the clinically used drugs flupirtine and tramadol under the same conditions.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10399490&dopt=Abstract tramadol Ultram

heinfo.net

AIM: To study the stereoselectivity in trans-tramadol [(+/-)-trans-T] metabolism and trans-O-demethyltramadol (M1) formation. METHODS: (+)-, (-)-, Or (+/-)-trans-T was separately incubated with rat liver microsomes in vitro. The concentrations of (+/-)-trans-T and M1 enantiomers were determined by high performance capillary electrophoresis (HPCE). RESULTS: When each enantiomer of (+/-)-trans-T was incubated with rat liver microsomes, the metabolic rate of (+)-trans-T was lower than that of (-)-trans-T. The kinetics of (+)-, (-)-M1 formation was found to fit the single-enzyme Michaelis-Menten model. The Vmax and CLint of (+)-M1 formation were lower than those of (-)-M1 formation. When (+/-)-trans-T was used as the substrate, the metabolic rates of (+)-, (-)-trans-T, and the formation rates of (+)-M1, (-)-M1 decreased to different extents. Dextromethorphan (Dex), propafenone (Pro), and fluoxetine (Flu) could inhibit both the metabolism of (+/-)-trans-T enantiomers and the formation of M1 enantiomers. Pro and Flu were shown to enhance the stereoselectivity in both (+/-)-trans-T metabolism and M1 formation, and Dex could only enhance that in M1 formation. CONCLUSION: (+/-)-Trans-T metabolism and M1 formation were stereoselective, (-)-trans-T being preferentially metabolized and (-)-M1 being preferentially formed. There was interaction in metabolism between (+/-)-trans-T enantiomers. Dex, Pro, and Flu had different effects on the stereoselectivity.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12511234&dopt=Abstract tramadol Ultram

posta.unizar.es

OBJECTIVE: To evaluate the risk of upper gastrointestinal bleeding associated with non-aspirin cardiovascular drug therapy, common analgesics and individual nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: The case group was made up of 1122 consecutive patients admitted with bleeding from a peptic lesion. The 2231 control subjects consisted of 1109 patients hospitalized for other reasons and 1122 outpatients from the same geographical area. The relative risk was calculated by unconditional logistic regression after adjusting for confounding factors. RESULTS: The use of the antiplatelet agent triflusal, and other commonly used cardiovascular drugs, such as beta-receptor blockers and calcium channel blockers, was not associated with increased risk of upper gastrointestinal bleeding. The use of angiotensin-converting enzyme inhibitors reduced the risk of bleeding by 30% (odds ratio 0.7; 95% confidence interval 0.5-0.96). Use of ketorolac (odds ratio 59.4; 95% confidence interval 7.7-454) and piroxicam (odds ratio 19.6; 95% confidence interval 9.3-35.3) carried the highest risk. Use of paracetamol and tramadol was not associated with increased risk of bleeding, but the non-narcotic agent metamizol was associated with a small increase in risk of upper gastrointestinal bleeding (odds ratio 2.6; 95% confidence interval 1.3-5.2). CONCLUSIONS: The use of the antiplatelet agent triflusal and other cardiovascular drugs apart from low-dose aspirin was not associated with gastrointestinal bleeding. The use of either NSAIDs or aspirin increased the risk of gastrointestinal bleeding but, among the analgesics, only metamizol induced a small increase in the risk of gastrointestinal bleeding.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12560762&dopt=Abstract tramadol Ultram

sj-user.he.cninfo.net

AIM: To investigate the transportation of the enantiomers of trans tramadol (trans T) and its active metabolite, O-demethyltramadol (M1) across blood-brain barrier. METHODS: Rats were sacrificed by femoral artery bleeding 1 h after i.p. administration of trans T hydrochloride, 16.7 mg.kg-1 or 50.0 mg.kg-1. Blood, cerebrospinal fluid and cerebral cortex were taken out. The enantiomers of trans T and M1 were analyzed by high performance capillary electrophoresis (HPCE). RESULTS: Among the three tissues, the concentration of each enantiomer of trans T and M1 was the highest in the cerebral cortex, and the lowest in the cerebrospinal fluid. In the serum, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of the enantiomers of M1 were similar. In the cerebrospinal fluid and cerebral cortex, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of (+)-M1 was lower than that of (-)-M1. CONCLUSION: The transportation across blood-brain barrier of the enantiomers of trans T and M1 was stereoselective. In the brain tissues, the concentrations of (+)-trans T and (-)-M1 were higher than those of their enantiomers.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12580098&dopt=Abstract tramadol Ultram




Eksp Klin Farmakol. 2002 Sep-Oct;65(5):50-2.
[Effect of droperidol and tramadol combination on the hemostasis in rabbits]

[Article in Russian]

Bol'shakov VV, Sapozhkov AV, Denisova SV.

Pharmacology Department, Kemerovo State Medical Academy, ul. Voroshilova 22A, Kemerovo, 650029 Russia.

The effect of a combined administration of analgesic droperidol and neuroleptic tramadol (tramal) on the plasma coagulation and platelet aggregation was studied on awake rabbits. Both tramadol and droperidol, as well as their combination, enhance the coagulation of plasma proteins and suppress the thrombocyte deaggregation process.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12596516&dopt=Abstract tramadol Ultram