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[General pharmacological studies on tramadol, a potent analgetic agent (author's transl)].

The general pharmacological properties of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal) are described and compared with those of other strong narcotic analgetics. In behavioral studies tramadol in high doses had a primarily stimulating effect in mice and rats and a sedative effect in rabbits and dogs. The Straub tail phenomenon, a reaction typical for mice administered morphine, was observed only after subtoxic doses of tramadol. In i.v. doses tramadol generally caused a weak central inhibition of non-stimulated and electrically stimulated brain activity in unanesthetized rabbits. Muscle tone and motor coordination in rats and mice were only slightly affected by the drug, in contrast to the effect of morphine. Unlike other strong analgesics tramadol in doses of 5--20 mg/kg i.v. did not cause respiratory depression and even clearly increased respiratory volume and rate in conscious rabbits and anesthetized dogs. In cats and dogs i.v. doses of tramadol up to 10 mg/kg were well tolerated in the cardiovascular system. Tramadol has a slight, papaverine-like spasmolytic effect and no effect on gastrointestinal motility or urinary and electrolyte excretion. The drug showed no antipyretic properties in rabbits. It inhibited edema in rats and guinea pigs but had no antiproliferative effect in the cotton pellet test in rats. Tramadol did not inhibit monoamine oxidase activity or cause enzyme induction in the rat liver.

Analgesics

Role of OPRM1 A118G polymorphism in tramadol analgesia following third molar surgery: a pharmacogenomic study.

BACKGROUND: The OPRM1 A118G (rs1799971) polymorphism has been implicated in interindividual variability in opioid analgesic response, but its influence on tramadol efficacy remains uncertain. This study evaluated the association between OPRM1 A118G and postoperative analgesic response to tramadol following mandibular third molar surgery. METHODS: In this prospective pharmacogenomic study, 53 adults undergoing impacted mandibular third molar extraction were enrolled. Genomic DNA was analyzed for OPRM1 A118G (rs1799971) using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). All procedures were performed under 2% lignocaine with adrenaline. Tramadol (50 mg) was administered after the onset of postoperative pain. Pain intensity was assessed using the Visual Analogue Scale (VAS) and Short-Form McGill Pain Questionnaire at 2, 4, and 6 hours. The primary outcome was summed pain intensity difference (SPID, 2-6 hours). RESULTS: Genotype frequencies were in Hardy-Weinberg equilibrium. No significant association was observed between OPRM1 genotype and SPID, VAS reduction, Pain Rating Index change, or responder status during the 6-hour observation period (all p > 0.05). CONCLUSION: OPRM1 A118G was not significantly associated with early tramadol analgesic response following third molar surgery. Larger studies incorporating both OPRM1 and CYP2D6 genotyping are needed to clarify the genetic determinants of tramadol analgesia as CYP2D6 gene is required for tramadol metabolism.

OPRM1

[The effect of tramadol in an open clinical trial (author's transl)].

1. The new analgesic drug 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal) was administered to a total of 840 patients by i.m. or i.v. injection or in suppository form in an open multi-center trial. The drug was found to be an effective and well-tolerated analgesic. 2. In all three forms of administration more than 80% of the patients treated rated the therapeutic efficacy of tramadol good to very good. In most cases the analgesic effect set in within 30 min and lasted 3--7 h. Tramadol was effective in relieving pain of various origins. 3. Serious side effects were not observed. The most frequent side effect was drowsiness. Transient hot flushes and outbreaks of sweating occurred occasionally following i.v. injection.

Adult

[Algo-pupillometric investigation of the analgesic effect of tramadol (author's transl)].

1. The analgesic efficacy of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal) (75 and 100 mg) was investigated in 22 young, healthy volunteers by means of an algo-pupillometric method. 2. Tramadal itself causes a slight miosis which becomes statistically significant only 3 h after administration. 3. In the algo-pupillogram the effect of tramadol is shown to be biphasic during the first 80 min. Thereafter the pupillary reaction steadily decreases, reaching a minimum after about 3.5--4 h in both dosages. 4. At the time of maximum effect the pupillary reaction of subjects given 75 or 150 mg tramadol is calculated to be equal to that of untreated individuals to whom only 60% or 10%, respectively, of the stimulus intensity has been applied.

Adult

[The effect of tramadol on the EEG and the electronystagmogram (author's transl)].

1-(m-Methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal) in oral doses of 150 mg/kg caused no essential changes in the EEG pattern in man. Only the alpha-rhythm of the occipital leads was more synchronized and the amplitude somewhat higher. beta-Waves increased slightly, but the delta-waves were not significantly changed. Tramadol induced no measurable alterations in the electronystagmographic recordings of quick voluntary eye movements or follow-up to-and-fro eye movements. In the optokinetic and postrotatory nystagmus, however, there was a moderate decrease in the total amplitude and maximal angular velocity of the slow nystagmic stage. The results of EEG and electronystagmographic investigations indicate that tramadol has a moderate relaxant (central depressant) effect.

Adult

[Clinical trial of tramadol by means of the "paired card" system (author's transl)].

1. 1-(m-Methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal) was administered i.v. to patients suffering from pain of various origins. Its efficacy and side effects were compared with those of metamizole and placebo. 2. Tramadol (100 mg) was as effective as metamizole (2.5 mg) and significantly more effective than placebo. 3. All three compounds showed no significant differences in type and number of side effects.

Analgesics

[The effect of tramadol, a new analgesic, on respiration and cardiovascular function (author's transl)].

1. The effect of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal), a new i.v. administered analgesic, on respiration and cardiovascular function was investigated in 15 patients in a clinic of general surgery. 2. Blood gas analysis revealed that tramadol, unlike morphine-like analgesics, does not depress respiration. 3. The drug did not affect blood pressure, and the observed slight increase in heart rate was transient and statistically not significant.

Analgesics

The effect of non-narcotic analgesic, tramadol, on cardiac contractility in dog.

The effect of a non-narcotic analgesic, tramadol, 5 mg/kg i.v. on cardiac contractility was studied in intact dog. The maximal intrinsic velocity of contraction of the ventricle, dP/dt/K P at P=O(Vmax) which is a most sensitive and reliable index of cardiac contractility, was decreased significantly 5 and 10 min after the injection, suggesting that the drug is a mild myocardial depressant at this dose and by this route.

Animals

[The effect of tramadol and other analgesics on the pain threshold in human dental pulp (author's transl)].

In 60 young, healthy volunteers the analgesic efficacy of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal), dextropropoxyphene and a commercial drug mixture (acetylsalicylic acid 200 mg; phenacetin 200 mg; codeine phosphor. 10 mg; caffeine anhydr. 50 mg; phenobarbital 25 mg) was investigated by determining the pain threshold in dental pulp. All three drugs increased the pain threshold considerably but there was no difference in the analgesic effect of the three drugs.

Adult

[Examination of psychic effects of a new analgesic agent of the cyclohexanols series. A contribution to a possible psychic dependence potential of tramadol (author's transl)].

A double-blind trial was performed with 30 male students of the University of Düsseldorf. The volunteers were divided at random into two groups containing 15 subjects each. One group received 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal), and the other placebo. The latter served as the controls. On three occasions at regular intervals in the course of one week the volunteers were questioned on the basis of Janke and Debus's "Eigenschaftswörterliste" (EWL) (attribution word list). The interviews were carried out 1 h after the injection (1 ampoule 100 mg i.m.). The results in the sense of any euphoretic or dysphoretic effects are discussed.

Adult