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)

The antiinflammatory, analgesic and antipyretic activities of 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0) were investigated in various animal models and compared with those of nimesulide, indomethacin and ibuprofen. The antiinflammatory potency of T-614 on carrageenin-induced paw edema, paper disk granuloma and established adjuvant arthritis was greater than that of ibuprofen, but slightly lower than those of nimesulide and indomethacin. In acute inflammatory models, unlike indomethacin, T-614 suppressed the edemas provoked by dextran and bromelain in rats, but its inhibitory action on ultraviolet erythema in guinea-pigs was weak. Although the analgesic activity of T-614 was hardly demonstrated in writhing tests in mice, its potency against the inflammatory pain such as Randall-Selitto test, adjuvant-induced hyperalgesia and antigen-induced arthritic pain in rats was superior to that of ibuprofen. Moreover, it had a potent analgesic effect on urate-induced synovitis in dogs. T-614 exerted a prompt and strong antipyretic effect in both yeast-induced febrile rats and lipopolysaccharide-induced febrile rabbits. T-614 had virtually no gastrointestinal ulcerogenic action and did not affect water and sodium excretion in rats. T-614 is a novel antiinflammatory compound with different pharmacological properties from that of the reference drugs.
 ...
PMID:Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne. 1st communication: antiinflammatory, analgesic and other related properties. 141 59

The anti-inflammatory, analgesic, and antipyretic effects and gastrointestinal toxicity of N-(3-[3-(piperidinylmethyl) phenoxy] propyl)- carbamoylmethylthio] ethyl 1-(p-chlorobenzoyl) 5-methoxy-2-methyl-3-indolylacetate (CP-331, CAS 127966-70-5), a new anti-inflammatory drug, were evaluated using indomethacin as a control. CP-331 exerted anti-inflammatory, analgesic and antipyretic effects on the models of carrageenin-induced paw edema, increased vascular permeability, ultraviolet light-induced erythema, granuloma proliferation, adjuvant arthritis, inflammatory pain, and yeast-induced fever. However, these effects were observed at a molar level similar to or higher than that of indomethacin. In addition, CP-331 influenced more markedly than indomethacin the delayed type hypersensitivity to sheep red blood cells. On the other hand, CP-331 did not damage the gastric mucosa even at a high dose of 1,000 mg/kg and also induced slighter damage to the intestinal mucosa than indomethacin. Thus, CP-331 exerted anti-inflammatory, analgesic, and antipyretic effects but without showing gastric toxicity, which is a common side effect of anti-inflammatory drugs. These results suggest the clinical applicability of this drug in the long-term therapy of inflammatory diseases such as rheumatoid arthritis.
 ...
PMID:Anti-inflammatory, analgesic, and antipyretic effects and gastrointestinal toxicity of the new anti-inflammatory drug N-(3-[3-(piperidinylmethyl)phenoxy]propyl)-carbamoylmethylthio ]ethyl 1-(p-chlorobenzoyl) 5-methoxy-2-methyl-3-indolylacetate. 141 61

Dimetindene maleate (DMM, Fenistil, CAS 3614-69-5) a specific H1-receptor antagonist, is therapeutically used for the treatment of respiratory allergies, urticaria, itching dermatoses and generally pruritic sensations occurring with various diseases. As it exhibits local anaesthetic activity in the rabbit cornea and the local anaesthetic activity of a couple of H1-antagonists was found to be linearly correlated to the H1-potency represented by the pA2-values--and dimethindene maleate demonstrates a high pA2-value--it seemed worth investigating the local anaesthetic potency in man making use of an objective and well validated pain model, the Laser algesimetry. The study was carried out with 24 healthy volunteers in a double-blind placebo- and reference-controlled, randomized, cross-over design. Three different medications were applied with occlusive dressing: DMM, lidocaine, and placebo. Selective thermo-noxious stimulation of A-delta- and C-fibers was induced by a CO2-laser. Somato-sensory evoked vertex potentials (SEPs) were simultaneously recorded. Both verum treatments showed a remarkable analgesic potency compared to placebo. Effects were preferably concentrated on the peripheral N1-component of the SEPs. The overall means of the N1-amplitudes were suppressed compared to placebo by both active drugs, with the effects being more pronounced for DMM.
 ...
PMID:Evaluation of the local anaesthetic activity of dimetindene maleate by means of laser algesimetry in healthy volunteers. 149 45

The general pharmacological properties of (-)-(S)-9-fluoro-2,3-dihydro-3- methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), an optically active isomer of ofloxacin, were examined. 1. Central nervous system (CNS): DR-3355 at 200-600 mg/kg p.o. showed depressant activity on the CNS, as was indicated by the depressant syndrome (mice), decreased spontaneous motor activity (mice) and hypothermia (mice and rabbits). In the cat behavior and EEG experiments, it had both stimulant and depressant effects at 30-100 mg/kg i.p., and caused transient slow waves followed by seizures at 20-30 mg/kg i.v. DR-3355 had no effect on convulsion, hexobarbital anesthesia, pain reaction to a tail pinch, or conditioned avoidance response, except that it showed mild analgesic activity in acetic acid writhing at 600 mg/kg p.o. 2. Respiratory and cardiovascular system: DR-3355 produced a hypotensive and a bradycardiac effect after the rapid i.v. injection of 6 mg/kg or more in anesthetized dogs, accompanied by an increase in plasma histamine concentration. Both changes were markedly reduced when the test drug was administered by continuous i.v. infusion. 3. Autonomic nervous system: DR-3355 inhibited nictitating membrane contraction induced by both pre- and post-ganglionic stimulation, and inhibited the depressor response to acetylcholine at 20 mg/kg i.v. It had no influence on pupil size or on pressor response to norepinephrine. 4. Gastrointestinal system: DR-3355 at 600 mg/kg p.o. inhibited gastric secretion. Dog gastrointestinal motility was slightly inhibited, and was then stimulated over the dose range of 2-20 mg/kg i.v. It had no influence on gastrointestinal propulsion, the gastric emptying rate or the gastric mucosa. 5. Isolated smooth muscle: At a concentration of 5 x 10(-4) g/ml, DR-3355 was devoid of spasmogenic or smasmolytic activity, except for showing a slight relaxation effect (trachea), inhibition of nicotine-induced contraction (ileum) and spontaneous or oxytocin-induced motility (pregnant uterus). 6. Miscellaneous: DR-3355 inhibited the urine output and carrageenin-induced paw edema at 600 mg/kg p.o. It had no effect on skeletal muscle contraction or the corneal reflex.
 ...
PMID:General pharmacology of the new quinolone antibacterial agent levofloxacin. 162 43

The pharmacokinetics and the relative bioavailability of a soluble granular form (sachets) of a pharmaceutical formulation containing ibuprofen (CAS 15687-27-1) and 1-arginine were investigated in healthy volunteers. Two granular dosage forms were evaluated, 200 and 400 mg, in comparison with the commercial equivalents (tablets). After the oral administration of both granular dosage forms, a quicker absorption and a significantly higher plasma bioavailability of ibuprofen in the first hour following the treatment than after tablets administration were observed. The mean values of peak plasma concentration (microgram/ml) were 26.1 and 56.4 after treatment with 200 and 400 mg sachets respectively vs. 16.3 and 43.0 after treatment with 200 and 400 mg tablets. The mean values of peak time were 16.9 and 24.4 min after treatment with 200 and 400 mg sachets respectively vs. 90.0 and 63.7 min after treatment with 200 and 400 mg tablets. The shortening in the absorption time and the increase in the plasma concentrations did not involve a quicker drug elimination nor cause any changes in the bioavailability (mean values of the relative bioavailability indexes of 0.98 for 200 mg dosage form and 1.02 for the 400 mg one). The analgesic activity of soluble ibuprofen 400 mg was compared with that of ibuprofen 400 mg tablets in patients with osteo-articular pain, according to a single dose, double-blind cross-over balanced design. The results showed that the soluble granular form is able to determine an analgesic effect significantly quicker and higher than that of tablets.
 ...
PMID:Activity and pharmacokinetics of a new oral dosage form of soluble ibuprofen. 164 82

The anti-inflammatory, analgesic, antipyretic and ulcerogenic activities of etodolac (CAS 41340-25-4), a new nonsteroidal anti-inflammatory agent, were compared with those of indometacin and other anti-inflammatory drugs in experimental animals. Etodolac had a remarkable anti-inflammatory effect in various experimental models: ultraviolet erythema, carrageenin-induced edema and swelling of adjuvant arthritis. In these models, the effective dose of etodolac was several fold that of indometacin. Etodolac inhibited prostaglandin E2 formation in a concentration-dependent manner, and its inhibitory potency was about 1/5 of that of indometacin. Etodolac also caused marked inhibition of granuloma formation and leucocyte functions such as chemotaxis, lysosomal enzyme release and active oxygen generation. These effects of etodolac were observed at similar doses of indometacin. Etodolac suppressed inflammatory pain but not non-inflammatory pain, and had an antipyretic effect but did not lower normal rectal temperature. Etodolac had no effect on delayed hypersensitivity reactions and was much less ulcerogenic than indometacin. These results indicate that etodolac is a low ulcerogenic anti-inflammatory agent with suppressing activities on leucocyte functions to the same extent as indometacin and prostaglandin biosynthesis.
 ...
PMID:Pharmacological properties of the new non-steroidal anti-inflammatory agent etodolac. 165 Oct 85

Pharmacological properties of midaglizole (DG-5128, CAS 66529-17-7) on central and peripheral nervous systems were investigated in comparison with those of tolbutamide. 1. Central nervous system: Midaglizole showed little or no effects on general behavior (mouse), spontaneous motor activity (mouse), hexobarbital anesthesia (mouse), conditioned avoidance response (rat) and body temperature (rabbit) at an oral dose of 100 mg/kg. It also produced little or no changes in electroencephalogram (cat) and spinal reflex (cat) after intravenous dosing of 10 mg/kg. The drug lacked anticonvulsant and analgesic activities (mouse). Midaglizole produced clonic convulsion, mydriasis, lacrimation, increase in pinna reflex, decrease in spontaneous motor activity, increase in pain threshold (mouse) and rise in body temperature (rabbit) at oral dose of 300 mg/kg. Tolbutamide showed similar effects except that it potentiated hexobarbital anesthesia, slightly decreased convulsion and tended to decrease body temperature. 2. Autonomic nervous system: Midaglizole potentiated the pressor response to norepinephrine and inhibited the depressor response to acetylcholine at an intravenous dose of 10 mg/kg (anesthetized dogs). Similar results were observed after dosing of tolbutamide. Midaglizole potentiated the contractile response of nictitating membrane to pre- and post-ganglionic cervical sympathetic nerve stimulation after intravenous dosing of 1 mg/kg (cat). Tolbutamide lacked the activity on the contraction elicited by both stimulations. Midaglizole and tolbutamide had little or no effect on pupil size (rabbit). 3. Skeletal muscle contraction (neuromuscular junction): Midaglizole (3-10 mg/kg i.v.) slightly potentiated the tibialis anterior muscle contraction induced by peroneal nerve stimulation, but did not potentiate the contraction by direct (muscle) stimulation (rabbit). On the other hand, tolbutamide increased the contraction induced by both nerve and muscle stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Pharmacological studies with the alpha 2-adrenoceptor antagonist midaglizole. Part II: Central and peripheral nervous systems. 167 69

The administration to rats of tryptophan (CAS 73-22-3) in high dosage causes a significant increase in pain threshold values. The analgesic effects of tryptophan are potentiated by allopurinol (CAS 315-30-0). The analgesic effects shown by tryptophan injection are associated with increased levels of serotonin and 5-hydroxyindoleacetic acid in some areas of the brain. The combined allopurinol and tryptophan treatment elevates the serotonin levels furtherly when they are compared with the values observed in animals receiving tryptophan only. The analgesia caused by tryptophan administration has been attributed to an increased activity of the serotoninergic system involved in the control of pain transmission.
 ...
PMID:Potentiation of the analgesic effects of tryptophan by allopurinol in rats. 172 97

Acetylsalicylic acid (CAS 50-78-2) (1000 mg orally) was investigated in a non-inflammatory experimental pain model in healthy male volunteers, selected for maximal homogeneity. Phasic pain was induced by intracutaneously applied electrical pulses of constant current. The nociceptive responses measured were, the pain ratings, the cerebral potentials and the EEG delta power in response to the stimuli. In addition, spontaneous EEG, auditory evoked potentials and reaction times were evaluated to determine effects upon the vigilance system. The study was performed in a placebo-controlled, double-blind repeated measures design. Blood samples were taken to monitor the plasma concentrations of the active agents. Acetylsalicylic acid produced clear analgesic effects in all pain relevant target variables. The effects increased with post-medication time, becoming significantly different from placebo 90 min after medication (p less than 0.01). At this time point the pain ratings were reduced by 4%, the pain related cerebral potentials by 15%, and the stimulus induced delta power of the EEG by 20%. These findings suggest a central action of acetylsalicylic acid by attenuation of experimentally induced nociceptive activity. No influences could be observed upon auditory evoked potentials, spontaneous EEG and reaction times. In other words, acetylsalicylic acid did not change vigilance by unspecific alterations of the CNS. The plasma concentration of acetylsalicylic acid reached mean values of 2.5 +/- 2.4 micrograms/ml within 25 min after oral medication, which remained constant during the entire post-medication period of 105 min. In contrast, the concentration of the metabolite salicylic acid increased steadily reaching mean values of 32.0 +/- 16.8 micrograms/ml at the end of the investigated period.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Central analgesic effects of acetylsalicylic acid in healthy men. 181 Feb 57

Aceclofenac (2-[(2,6-dichlorophenyl) amine]phenylacetoxyacetic acid; CAS 89796-99-6) is a new orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid group which showed remarkable anti-inflammatory, analgesic, and antipyretic properties. Hence, aceclofenac possesses a potent inhibitory activity in several models of acute and chronic inflammation in rodents, and resembles indometacin and diclofenac in its pharmacodynamic profile, being superior to naproxen and phenylbutazone. In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically. The analgesic effect of aceclofenac on the pain elicited by chemical and mechanical stimuli was nearly equal to or slightly better than that of indometacin and diclofenac. Fever induced by brewer's yeast injection in rats was also markedly suppressed by aceclofenac. In contrast, the acute gastric ulcerogenic activity of aceclofenac was about 2, 4 and 7-fold lesser than that of naproxen, diclofenac, or indometacin, respectively. As a consequence of its high anti-inflammatory activity and lower potential for gastric damage aceclofenac exhibited the most favourable therapeutic ratio in comparison with indometacin, diclofenac, naproxen, and phenylbutazone. These data indicate that aceclofenac could be a potent anti-inflammatory and analgesic agent with a wide margin of safety in clinical practice.
 ...
PMID:Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac. 181 28


1 2 3 4 5 6 7 Next >>