Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several animal studies have demonstrated that pain is modulated by spinal mechanisms involving prostaglandins and that acetylsalicylic acid (ASA) administered intrathecally has an analgesic effect. We report our experience of this treatment in 60 patients with proven and advanced cancer. An isobaric solution of lysine acetylsalicylate was administered by lumbar puncture in doses ranging from 120 to 720 mg of ASA. The results were evaluated using the habitual criteria: scoring system, behaviour, consumption of analgesic drugs. In this trial the method proved astonishingly effective (78% of the cases). Analgesia was strong, almost immediate and without influence on motricity. No thermic or neurovegetative changes were noted. The effect of one injection lasted from 3 weeks to 1 month on average; it was reproduced and often more prolonged after a repeat injection. Pain associated with bone metastases seems to constitute the best indication, notably in breast and lung cancer and in myeloma. Visceral (pancreas) or neural pain requires higher doses to respond. Failures (22%) were due to such factors as insufficient dosage at the very beginning of our experience or severe depressive syndrome. The perineal and sphincteral pain of rectal cancer often resists treatment. This simple, inexpensive and very effective method with no other complication than a frequent tendency to fatigue should rank among other analgesic measures in cancer. The lack of respiratory depression is a major advantage over catheter spinal opiate analgesia. We consider that its main indications are pain associated with osteolytic metastases of adenocarcinomas, and myelomas. Owing to the absence of formal toxicological data, its use must be limited to cancer pain and to patients with a life expectancy of less than 2 years.
 ...
PMID:[Chronic refractory pain in cancer patients. Value of the spinal injection of lysine acetylsalicylate. 60 cases]. 295 75

The effects of centrally administered kentsin (H-Thr-Pro-Arg-Lys-OH) on intestinal motility and on pain perception were investigated in rats chronically equipped with lateral ventricle catheters. Intestinal motility was recorded electromyographically from electrodes placed on the duodeno-jejunum; analgesia was evaluated by the hot-plate and tail-flick tests. Kentsin (4.0 ug/kg), injected intracerebroventricularly (ICV) 2 hours after the beginning of a meal, restores the "fasted" i.e. the migrating myoelectric complex of intestinal motility, while a 5 times higher dose administered subcutaneously was inactive. The ICV effect of kentsin was blocked by previous ICV administration of naloxone (400 ug/kg). In contrast, kentsin administered ICV (40 ug/kg) or SC (200 ug/kg) did not affect significantly (P greater than 0.05) the time latency in the two analgesic tests during 90 minutes after its administration and did not significantly modify the analgesic effects of (D5-Ala2, Met5) enkephalinamide. We conclude that kentsin when centrally administered acts on opiate receptors to alter gastrointestinal motility but without effects on pain perception.
 ...
PMID:A tetrapeptide isolated from hamster embryo with central opiate properties on gastrointestinal motility but not on pain perception. 301 51

The effects of lysine acetylsalicylate, a new injectable salicylate, on postoperative pain relief and platelet function were studied in ten men who had surgery for peptic ulcer. Four of five patients receiving lysine acetylsalicylate had satisfactory pain relief. One patient required an additional injection of 15 mg of pentazocine. Of the five patients in the control group, an average (+/- SD) dose of 90 +/- 23.7 mg of pentazocine was required to achieve adequate postoperative pain relief. Lysine acetylsalicylate decreased platelet aggregability but without resulting in hemorrhage. We concluded that this new salicylate administered intravenously to patients in the postoperative period provided adequate analgesia while allowing effective hemostasis despite its inhibitory effect on platelet aggregation.
 ...
PMID:Postoperative intravenous administration of lysine acetylsalicylate: effect on pain relief and platelet function. 310 86

Thirty elderly patients (mean age 74) with osteoarthritis effecting various joints were treated with an oral suspension of either tiaprofenic acid (TA) (600 mg per diem b.i.d.) or lysine acetyl salicylate (1800 mg per diem b.i.d.) for 3-6 months in an open randomized experimental study. The parameters of efficacy assessed were pain at rest and under load, stiffness, ability to perform a pre-selected daily exercise and joint movements hampered by the disease. Blood flow, liver and kidney function and side effects were examined on a monthly basis. The tiaprofenic acid proved more effective in reducing pain and aiding functional recovery and was also better tolerated, especially at gastrointestinal level. Nine patients under lysine acetyl salicylate and 2 under tiaprofenic acid were forced to suspend treatment due to pyrosis, epigastralgia ed dyspepsia.
 ...
PMID:[Comparative clinical study of tiaprofenic acid and lysine acetylsalicylate in aged osteoarthrosis patients]. 311 Jun 54

Pyrazolone and salicylic acid derivatives and the aniline derivative, paracetamol, are often classified as peripherally acting analgesic agents, while morphine is a centrally acting analgesic agent. Since indications exist that the non-opioid analgesic agents can also produce central effects, experiments were carried out on rats under urethane anaesthesia in which activity was recorded from single neurones in the dorsomedial part of the ventral nucleus (VDM) of the thalamus that was elicited by supramaximal electrical stimulation of nociceptive afferents in the sural nerve. In addition, activity was recorded in ascending axons of the spinal cord which was evoked by electrical stimulation of nociceptive afferents in the sural nerve. The substances studied were morphine, the pyrazolone derivatives, metamizol (dipyrone) and aminophenazone ('Pyramidon'), lysine acetylsalicylate, and paracetamol. All drugs were found to depress dose-dependently evoked activity in VDM neurones after intravenous (i.v.) injection. The ED50 of morphine in depressing evoked activity in VDM neurones is 0.05 mg/kg. Morphine also dose-dependently reduced activity in ascending axons of the spinal cord, the ED50 being 1.7 mg/kg. The ED50 of metamizol in depressing evoked activity in VDM neurones is 120 mg/kg, and that of aminophenazone is 22.7 mg/kg. The 2 ED50 values differ significantly. It has been found previously that metamizol increased nociceptive activity in some ascending axons and aminophenazone increased this activity in all ascending axons tested. The ED50 of lysine acetylsalicylate in depressing evoked activity in VDM neurones is 74 mg/kg. The drug did not reduce nociceptive activity in ascending axons of the spinal cord. The ED50 of paracetamol in depressing evoked activity in VDM neurones is 19.0 mg/kg. Paracetamol did not depress nociceptive activity in ascending axons of the spinal cord at a dose as high as 150 mg/kg administered by intraperitoneal injection. Naloxone (0.2 mg/kg i.v.) abolished the depressant effects of morphine but failed to reduce those of the non-opioid analgesic agents even at a high dose (1 mg/kg i.v.). Unlike morphine, the non-opioid analgesic agents did not completely block evoked activity in VDM neurones but only partially blocked their activation. The results suggest that the non-opioid analgesic agents tested can produce a central analgesic effect which, however, is weaker than that of morphine.
Pain 1988 Mar
PMID:Depression by morphine and the non-opioid analgesic agents, metamizol (dipyrone), lysine acetylsalicylate, and paracetamol, of activity in rat thalamus neurones evoked by electrical stimulation of nociceptive afferents. 312 87

The analgesic effect, acute toxicity and pharmacokinetics of lysine acetylsalicylate (LAS), a water-soluble salt of acetylsalicylic acid (ASA) were studied as compared with a 50% solution of analgin and a 4% solution of amidopyrine at intramuscular administration and ASA administered intragastrically. During inflammation-induced pain in rats LAS exerts a pronounced analgesic effect exceeding the activity of other agents. LD50 of LAS was similar to that of analgin and ASA. LAS toxicity was significantly less than that of amidopyrine. Bioavailability of ASA at intramuscular administration to rabbits was close to that at intravenous injection and significantly higher as compared with intragastric administration.
 ...
PMID:[Analgesic action and pharmacokinetics of lysine acetylsalicylate administered intramuscularly]. 314 14

General pharmacological effects of N2-[(N-acetyl-muramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-ly sine MDP-Lys(L18), muroctasin) were examined and the following results were obtained. 1. Central nervous system: MDP-Lys(L18) had no effect on behavior, spontaneous motor activity, electroshock- and chemoshock-induced convulsions, hexobarbital sleeping time, pain threshold (mice), conditioned avoidance response (rats) at a dose of 0.4 mg/kg, s.c. and EEG as well as spinal reflex (cats) at a dose of 0.4 mg/kg, i.v. It produced a significant elevation in body temperature (rabbits) at doses of 13 micrograms/kg, s.c. and greater. 2. Respiratory and cardiovascular system (dogs): MDP-Lys(L18) did not show any significant effect on respiratory and cardiovascular functions at a dose of 0.4 mg/kg i.v. 3. Autonomic nervous system: MDP-Lys(L18) induced a miosis (rabbits) at doses of 13 micrograms/kg s.c. and greater. It did not affect norepinephrine-induced pressor and acetylcholine-induced depressor responses (dogs) and contraction of the nictitating membrane induced by electrical stimulation (cats) at a dose of 0.4 mg/kg i.v. 4. Smooth muscles: In the experiments using the isolated ileum, vas deferens, trachea (guinea pigs) and uterus (rats), MDP-Lys(L18) showed neither spasmogenic nor spasmolytic activity at a concentration of 4 x 10(-6) g/ml. Gastrointestinal propulsion (mice), gastric mucosa, gastric emptying rate and gastric secretion (rats) were not affected by this drug at a dose of 0.4 mg/kg s.c. MDP-Lys(L18) did not influence gastrointestinal motility (dogs) at a dose of 0.4 mg/kg, i.v. 5. Miscellaneous: MDP(L-18) suppressed carrageenan-induced edema (rats) at doses of 0.13 mg/kg s.c. and greater.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:General pharmacological properties of muroctasin. 319 Jul 91

Local endometrial blood flow was measured by a thermistor technique and myometrial activity by intrauterine pressure recording in 10 women before and during menstruation. The effect of lysine vasopressin infusion (1 pmol/kg body-weight per min) and of bolus injection of a synthetic oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (10 nmol/kg body-weight), were studied. Spontaneous variations in blood flow were seen synchronous with clearly demarcated uterine contractions, the myometrial activity being significantly increased in early (day -1 to day +2) compared with late (day +3 to day +5) menstrual phase. The vasopressin infusion decreased blood flow, stimulated uterine activity and caused slight to moderate dysmenorrhoea-like pain. These effects were completely inhibited by the injection of the oxytocin analogue. In-vitro studies on uterine arteries confirmed that the analogue also inhibited the vasopressin-induced constriction of the uterine arteries. This antagonist was more effective than two other analogues, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-oxytocin and 1-deamino-2-Tyr(OEt)-oxytocin. The counteracting effect of 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on the vasopressin-induced decrease of blood flow and increase of contractions supports the therapeutic value of the drug in primary dysmenorrhoea and preterm labour.
 ...
PMID:Uterine blood flow and myometrial activity at menstruation, and the action of vasopressin and a synthetic antagonist. 319 Oct 63

Intermittent claudication is associated with adaptation in muscle metabolism. This study has evaluated the metabolism of amino acids at rest and during non-steady state exercise in patients with arterial insufficiency of at least six months duration in comparison with matched control individuals. The exchange of amino acids were measured during two periods of acute exercise; one initial exercise period with a standardized work load and exercise time and a second exercise period which continued until further exercise was impossible due to pain in the patients and exhaustion in the controls. The maximum blood flow was reduced by 40% in the patients but the maximum oxygen uptake per unit power developed was almost the same in patients and controls. The patients had significantly lower concentrations of glutamine, lysine and taurine at rest compared with the controls. The exchange of amino acids across the resting leg did not differ between the two groups. Exercise increased the efflux of amino acids in both patients and controls. The efflux of glutamine (896 +/- 205 vs. 48 +/- 359 nmol/100 ml/min/watt) was higher in the patients compared to the controls at the first exercise period with inverse changes in the opposite direction of asparagine (149 +/- 105 vs. 799 +/- 121 and 27 +/- 70 vs. 633 +/- 334 nmol/100 ml/min/watt at the first and second exercise, respectively. Alanine release did not differ between the groups. The complementary patterns of glutamine and asparagine during hypoxic exercise in the patients may reflect the fact that these amino acids share a common carrier system. The similarity in the efflux of non-metabolized amino acids, such as methionine, phenylalanine, tyrosine and 3-methylhistidine, indicated that muscle hypoxia in claudication patients did not promote net degradation of either globular or myofibrillar proteins, although exercise increased the efflux of 3-methylhistidine three- to fourfold in both patients and control individuals (from 1 +/- 0.4 to 4 +/- 1.8 and from 0 +/- 0.7 to 6 +/- 2.5 nmol/100 ml/min/watt, respectively). The exercise-induced alterations in leg exchange of amino acids were restored within 10-20 min following exercise regardless of hypoxia. The results demonstrate that patients with arterial insufficiency have altered intermediary metabolism of amino acids during exercise. However, muscle hypoxia in such patients does not seem to promote a negative protein balance or induce serious alterations in cell membrane integrity.
 ...
PMID:Leg exchange of amino acids during exercise in patients with arterial insufficiency. 340 84

Mafosfamide is a new oxazaphosphorine that breaks down spontaneously into 4-hydroxy-cyclophosphamide. A phase I trial with cyclohexylamine and lysine salts of mafosfamide was carried out in 16 patients, using weekly IV perfusion. Dose-limiting toxicities were not hematological, but consisted in the development of severe pain along the vein during administration. A particular mucosal syndrome with sneezing and conjunctivitis was seen only after administration of the lysine salt. The dose of 700 mg/m2 per week represents the maximum tolerated dose with this weekly schedule.
 ...
PMID:Phase I study of cyclohexylamine and lysine salt of mafosfamide. 351 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>