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At least 19 recordsLinked to original sources

PubMed1986

Evaluation of tilidine for morphine-like subjective effects and euphoria.

Tilidine is an opioid analgesic that has been abused predominantly by the oral route. Studies of parenterally administered tilidine in animals did not clearly indicate a dependence potential of the morphine type. In this study we examined the abuse potential of orally and parenterally administered tilidine in humans. Both orally and intramuscularly given tilidine produced miosis and morphine-like subjective effects in non-dependent subjects. Oral tilidine was 1/8-1/10 as potent and intramuscular tilidine was 1/22 as potent as parenteral morphine in producing morphine-like subjective and miotic effects. Intramuscular tilidine suppressed and did not precipitate signs of abstinence in morphine-dependent subjects. However, intramuscularly given tilidine produced toxic effects not seen with morphine. Meperidine, codeine and d-propoxyphene produced morphine-like subjective and miotic effects, but also produced toxic effects at the highest doses tested. The results suggest that tilidine has a potential to be abused, that this potential is less than that of parenteral morphine and that tilidine is more likely to be abused orally than by the intramuscular route.

Administration, Oral↗

PubMed1978

[Critical comments on a case history "a death case involving tilidine" (author's transl)].

The author looks critically at the description of a suicide case involving a barbiturate dose that could not be determined exactly and doses of hydroxyzine and tilidine. Drugs with a short and a medium short duration of action obviously had the greatest effect. There was no description of an investigation of the gastric contents. The concentration of barbiturates in the blood alone was sufficient to cause death. The deceased also took hydroxyzine, and then finally 750 mg tilidine in capsule form. Tilidine's action is relatively slow in onset. The author discusses tilidine's possible contribution to the cause of death and comes to a different conclusion from the authors of the case report, especially as regards the key words "Tilidine--Intoxication". The authors of the case report ought to have called it "A Death Case Involving Barbiturates, Hydroxyzine and Tilidine" rather than giving is such a suggestive title as "A Death Case Involving Tildine". This would have been a more accurate representation of the facts and would have assisted the reader to grasp the complex toxicological situation more clearly.

Barbiturates↗

PubMed1975

The interaction of tilidine and pethidine in postoperative pain.

The mode of interaction between the new, non-narcotic analgesic tilidine and pethidine was studied in the treatment of postoperative pain. The potency ratio 3:1 (pethidine:tilidine) found previously was used in the comparison. Thus 0.25 mg/kg of pethidine with 0.75 mg/kg of tilidine and 0.5 mg/kg of pethidine with 1.5 mg/kg of tilidine were compared with 0.5 mg/kg and with 1.0 mg/kg of pethidine. These drug combinations proved to be equipotent with the pethidine dosages used. Consequently the mode of interaction seemed to be additive synergism. The onset of action was slightly faster with pethidine, but the duration of action was longer with pethidine-tilidine combinations. Respiratory depression and sedation were less evident after pethidine-tilidine combinations than after equianalgesic doses of pethidine. Circulatory effects were similar in all groups. No statistical difference in other side effects could be demonstrated between the groups.

Adolescent↗

PubMed1977

[Double-blind study on the analgesic efficacy of tilidine (valoron) and pethidine (dolantin) in gastro-intestinal endoscopies and liver biopsies (author's transl)].

In a double-blind trial involving 99 patients, equi-analgesic doses of tilidine and pethidine (100 mg of each i.m.) were compared as to their effectiveness in laparoscopies, gastroscopies, esophagoscopies and liver needle biopsies. The two substances produced equally analgesic effects both during and after the various procedures, with the exception of the liver biopsies, in which tilidine was shown to be significantly more effective than pethidine. Whereas no sedation was noted in connection with tilidine medication, pethidine produced a marked, undesirable sleepiness in 12% of the cases observed. Due to the high analgesic efficacy and tolerance of tilidine found in both this and numerous other clinical trials and to its particular advantages over pethidine and other opiates (no respiratory depression, no effect on intestinal motility) tilidine can be recommended for premedication in gastrointestinal endoscopies and liver needle biopsies. Tilidine (Valoron) is not subject to the restrictions imposed by the West German narcotics laws.

Analgesia↗

PubMed1977

A clinical comparison of tilidine hydrochloride and pentazocine, given orally for the treatment of postoperative pain.

A controlled, double-blind study involving 250 women was carried out ot assess the efficacy of oral tilidine 25, 50 and 100 mg in treating postepisiotomy pain, and to offer a comparison with oral pentazocine 50 mg. All the analgesics produced significant pain relief. At peak effect tilidine 50 mg produced very similar results to pentazocine 50 mg with tilidine 25 mg producing less, and tilidine 100 mg more pain relief. These results were not, however, statistically significant. In these postdelivery ambulant patients pentazocine 50 mg and tilidine 100 mg produced at 25% incidence of side-effects, mainly dizziness and drowsiness, but tilidine 25 mg produced significant analgesia with virtually no side-effects.

Administration, Oral↗

PubMed1986

Negative reinforcing properties of naloxone in the non-dependent rhesus monkey: influence on reinforcing properties of codeine, tilidine, buprenorphine, and pentazocine.

Scheduled infusions of naloxone (1-100 micrograms/kg/inf.) and of buprenorphine (250 micrograms/kg/inf.) generated drug avoidance behavior in the non-dependent rhesus monkey under a continuous avoidance-escape paradigm. Pentazocine (1-100 micrograms/kg/inf.) codeine, (1-100 micrograms/kg/inf. and tilidine (1-250 micrograms/kg/inf.) were ineffective. Addition of varying doses of naloxone to scheduled infusions of codeine, tilidine, and pentazocine generated avoidance behavior not present with scheduled infusions of these opioids alone. The naloxone doses necessary for generation of avoidance behavior were low with the agonists codeine and tilidine, higher with the weak antagonist pentazocine, and highest with the strong antagonist buprenorphine. When monkeys were presented with the fixed tilidine-naloxone combination (100 + 8 parts) and pentazocine-naloxone combination (100 + 1 part) and the buprenorphine-naloxone combination (100 + 66 parts) presently in clinical use only the tilidine-naloxone combination generated drug avoidance behavior to an appreciable extent.

Animals↗

PubMed1978

The opiate-like action of tilidine is mediated by metabolites.

The analgesic effect of tilidine in rats is completely antagonized by the narcotic antagonist naloxone. Radioreceptor assays revealed, however, that the main metabolites of tilidine, nortilidine and bisnortilidine, rather than tilidine exhibit affinity to opiate receptors. These findings were confirmed in studies using the electrically stimulated guinea pig ileum and the mouse vas deferens. Chronic tilidine administration to rats caused a considerable degree of physical dependence, which was expected from the ability of the intact animal to metabolize tilidine. In the isolated ileum from chronically morphinized guinea pigs, both nortilidine and bisnortilidine fully substituted for morphine in preventing induction of withdrawal, indicating dependence liability of these metabolites.

Analgesia↗

PubMed1978

Tilidine abuse and dependence.

Tilidine (Valoron) is a new strong analgesic which was introduced into the market in West Germany in 1970. In February 1978 tilidine was placed under the regulations of the German Narcotics Act because it had rapidly become an easily acquired substitute for opiates on the drug scene. Cases have become known where tilidine dependence developed during the treatment of pain in patients without any preceding addiction to other drugs. The relevant literature on tilidine is reviewed in regard to pharmacological, epidemiological and clinical aspects of tilidine dependence and abuse.

Adult↗

PubMed1976

[ On the metabolism of ethyl-DL-trans-2-dimethylamino-1-phenyl-cyclohex-3-ene-trans-1-carboxylate-hydrochloride (Tilidine-HCl). 2nd Communication: Studies with 14C-labelled substance on rats and dogs].

Absorption, distribution, metabolism and excretion of the potent analgesic ethyl-DL-trans-2-timethylamino-1-phenyl-chclohex-3-ene-trans-1-carboxylate-hydrochloride (tilidine-HCl, Gö 1261 C, active ingredient of Vloron) were investigated in rats and dogs, using the radioactively labelled substance. Following oral administration, tilidine-HCl is rapidly and completely absorbed from the duodenum. During absorption, tilidine undergoes a marked first-pass effect. In plasma several metabolites are found, part of them occurring in higher concentrations than the unchanged substance. The metabolites are also formed rapidly after parenteral administration, unchanged tilidine being found in higher concentrations than any of the metabolites at all times measured. Following both routes of administration, the Met. I (nortilidine), also possessing a strong analgesic activity, reaches similar plasma levels. 14C distribution studies in rats showed a relatively high concentration of the radioactivity in the excretory organs, liver and kidneys. In brain, muscle tissue and blood much lower 14C concentrations are found. The concentrations measured in the foetal organs correspond to those in the muscle tissue of the mother animals and are, therefore, much lower than in most maternal organs. The radioactivity is eliminated from the foetal organs at the same rate as from the maternal organs. Tilidine is rapidly and completely eliminated with the excrements, nearly exclusively in the form of metabolic products. Rats eliminate 50% of the given radioactivity via the kidneys. The relatively high fecal elimination is based on the biliary metabolites. Following intraduodenal and intravenous administration to rats with an interrupted enterohepatic circulation, about 80% of the dose is eliminated with bile. The biliary metabolites are partly reabsorbed. In dogs, approx. 80% of the applied radioactivity is eliminated with urine.

Administration, Oral↗

PubMed1986

Evaluation of chronic toxicity and carcinogenesis in rodents with the synthetic analgesic, tilidine fumarate.

The carcinogenic potential of tilidine fumarate, a synthetic analgesic, was studied for 80 and 104 weeks in mice and rats, respectively. Groups of 50 albino CF1 mice and 65 albino Wistar rats of each sex received tilidine fumarate-lactose blend (1:1) at doses of 100, 40 and 16 mg/kg. The control groups consisted of 100 mice and 115 rats of each sex and received the lactose vehicle only. Treatment-related non-neoplastic changes consisted of reversible, increased cytoplasmic eosinophilia of hepatocytes in high and mid dose rats corresponding to areas of proliferating smooth endoplasmic reticulum; and an increased incidence in high dose rats of proliferative or cystic lesions of the biliary epithelium. Adequate survival rates allowed stringent statistical analysis of neoplasia. Tilidine did not evoke increased tumor incidences or changes in the average latency or onset of tumors in either species. The most frequent tumors represented spontaneous neoplasia characteristic of historical background incidence in these strains. In mice, the only statistically significant (P less than 0.01) variation in tumor incidence was an increased rate of lung alveologenic adenocarcinomas in females at 100 mg/kg (24%), compared with the concurrent untreated controls (10%), but without a statistically significant difference from historical control data (27%). Female rats given 100 mg/kg showed statistically significant (P less than 0.01) decreased incidences of mammary fibroadenoma and pituitary adenoma. From these data, it was concluded that the synthetic analgesic tilidine does not possess tumorigenic potential in rodents.

Administration, Oral↗

PubMed1991

[Analgesia using oral administration of tilidine naloxone for extracorporeal shockwave lithotripsy. A double blind study].

Reduction in pain perception during ESWL due to a technical modification of the lithotriptor was expected and prompted a reassessment of anaesthesia techniques for ESWL. In this study the need for analgesic treatment had to be investigated. After satisfactory preliminary results in a previous pilot study, the value of the oral combination of the anti-anxiety drug dipotassium clorazepate on the evening before ESWL together with the analgesic tilidine-naloxone before treatment was tested in a randomised double-blind study in 120 patients. In case of intolerable pain during the treatment all patients were free to ask for additional intravenous analgesic medication (fentanyl). During ESWL, 28.3% of the tilidine-N group patients and 6.7% of the placebo group were pain-free, whereas intolerable pain was reported by 30% of the tilidine-N group and 56.7% of the placebo group. Therefore, 70% of the tilidine-N group patients were treated without any additional analgesic or sedative medication. The good experience with this oral anaesthesia approach, the lack of significant side effects and a good acceptance by the patients warrant further recommendation of this technique.

Administration, Oral↗

PubMedDate not supplied

Disposition of tilidine in a fatal poisoning in man.

A fatal intoxication due to the ingestion of tilidine, a narcotic analgesic, in conjunction with ethanol, is described. Tilidine and its two active metabolites, nortilidine and bisnortilidine, were identified and quantitated in the biological fluids and tissues by thin-layer chromatography (TLC), gas-liquid chromatography with sensitive nitrogen-phosphorus detection (GLC/NPD) and gas-liquid chromatography with mass spectrometric detection (GC/MS). The toxicological results are compared with previously reported 14C-tilidine tissue distributions in rats following oral administration and limited tissue data in a previously reported human fatality. In the present case, the death was attributed to the combined central nervous system-depressing effects of ethanol and tilidine.

Adult↗

PubMed1976

[Premedication with valoron (Tilidin) in internal laparoscopy].

Apart from sufficient experience on the part of the examining physician and adequate technical apparatus, proper premedication can facilitate the procedures for both patient and physician considerably. The paper reports on experience gained in 500 laparoscopies carried out under conditions which were deviated slightly from those hitherto recommended in the literature. The analgesic employed was Tilidine (in Germany: Valoron), and Diazepam was used as a sedative; both of these substances were given intravenously, the vein was kept open for the entire course of the examination. The Tilidine dose was normally 50-100 mg, but under exceptional circumstances as much as 150 mg. Tilidine showed good analgesic effectiveness and tolerance; no case or nausea or vomiting and no sign of respiratory depression of effects on smooth muscle were observed under the conditions stated. The fact that Tilidine is not subject to the restrictions imposed by the German narcotics law is also seen as an advantage. The Diazepam dose was 5-30 mg. Apart from its sedative effect Diazepam also diminishes the tonus of skeletal muscle (important in laparoscopy) and has a relatively long time of elimination (20-48 h). In addition to these two substances, 10-20 ccm of 1% Lidocaine solution with Epinephrine additive was given as a local anaesthetic. The investigators' experience with the above premedication procedure was found to be convincingly positive.

Anesthesia, Local↗

PubMed1975

[The effect of tilidine on left-ventricular function of the human heart (author's transl)].

The effect of tilidine (Valoron, 1.5 mg/kg) on left-ventricular function was measured in ten patients undergoing diagnostic cardiac catheterization. In the course of thirty minutes after administration there was a small fall in systemic arterial pressure, decrease in cardiac output, cardiac index and stroke volume, as well as a change in the isovolumetric inotropic state. Haemodynamic and inotropic changes were small in amount, varying between 3.4 and 14.5% of basal values. This study indicates that tilidine, while having a powerful analgesic effect, has only a mild contractility-inhibiting action. Tilidine is thus a useful alternative as an analgesic in cardiac pain.

Adult↗

PubMedDate not supplied

In vitro adsorption of tilidine HCl by activated charcoal.

In vitro studies were carried out in order to determine the adsorption of tilidine HCl, a narcotic analgesic, by activated charcoal (max. adsorption capacity 185.5 mg/g of charcoal). The path of the adsorption isotherms at pH 1.2 and 7.5 suggests that the in vivo adsorption of tilidine HCl may be increased when the drug passes from the stomach to the intestine, unless the intestinal content exerts a displacing effect. Nevertheless, the adsorption was dependent on the quantity of activated charcoal used, becoming more complete when the quantity of activated charcoal was increased. The effects of additives on the adsorption capacity of activated charcoal were also investigated in vitro. Ethanol, sorbitol and sucrose significantly reduced drug adsorption, while cacao powder, milk and starch had no effect on tilidine adsorption. At an acid pH, Federa Activated Charcoal significantly adsorbed more drug than either Norit A or Activated Charcoal Merck.

Adsorption↗

PubMed1976

Action of tilidine hydrochloride and morphine hydrochloride on ventilatory control in normal subjects.

The action of tilidine hydrochloride and morphine hydrochloride on the ventilatory response to inhaled carbon dioxide has been assessed in 10 normal volunteers. In doses of 50 mg and 100 mg given intravenously, tilidine hydrochloride induced less respiratory depression than 10 mg of morphine given intravenously. Side effects were not different or troublesome with either drug. Depending on its relative pain-relieving property, tilidine hydrochloride may have advantages over morphine as an analgesic.

Adult↗

PubMed1978

Gas-chromatographic determination of nanogram amounts of enantiomers of nortilidine, a main metabolite of tilidine, in biological specimens.

We report a specific and sensitive method for determination of the individual optical isomers of nortilidine, a main metabolite of tilidine, with the aid of a nitrogen-sensitive detector. With N-trifluoroacetyl-L-leucyl chloride as chiral reagent, the diastereomeric derivatives of the nortilidine enantiomers could be separated and quantified in the nanogram range. Under these conditions, the enantiomers of bisnortilidine, another main metabolite of tilidine, were also separated. Investigations in rats with the enantiomers of tilidine and nortilidine indicated that no racemization occurs during N-demethylation in the organism. After oral and intravenous administration of 50 mg of tilidine.HCI to a human volunteer, identical concentrations of nortilidine enantiomers were found in the plasma.

Animals↗

PubMed1978

[Effects of tilidin and naloxone on pulmonary function (author's transl)].

The respiratory depressant effect of tilidine (valoron) was investigated in anaesthetized patients. One hundred mg of tilidine had a slight respiratory depressant effect which was without importance in awake subjects. The respiratory depression caused by tilidine could be antagonized by naloxone while the analgesic effect was maintained. This suggests a dissociation of the mechanisms responsible for the respiratory and the analgesic actions.

Adolescent↗