salicylates and imidazole-2-hydroxybenzoate

Imidazole-salicylate is a non-steroidal anti-inflammatory drug with limited inhibitory effects on prostaglandin synthesis. The renal effects of this drug were investigated by a double-blind cross-over study in 10 patients with cirrhosis and ascites. Two therapeutic doses of imidazole-salicylate (750 mg each) were given at midnight and 08:00 h and 80 mg of furosemide were injected intravenously at 09:00 h. The same procedure was followed on another day but a placebo replaced imidazole-salicylate. Renal function (creatinine clearance, free water and electrolyte excretions) and urinary excretion of prostaglandin E, 6-keto-prostaglandin F1 alpha and thromboxane B2 were evaluated for 8 h after the first dose of the drug and for 2 h after furosemide injection. Platelet thromboxane production was also determined 9 h after the first administration of drug or placebo. Imidazole-salicylate did not affect renal function or inhibit kidney prostanoid production either under basal conditions or after the stimulating effect of furosemide. On the contrary, imidazole-salicylate significantly inhibited platelet thromboxane production (45.8 +/- 9 vs. 69.4 +/- 7.5 ng/ml, P < 0.05). These results suggest that imidazole-salicylate is an anti-inflammatory drug that can be given to patients with decompensated cirrhosis without risk of inhibiting kidney prostaglandin synthesis or the renal response to furosemide.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Ascites; Blood Platelets; Diuretics; Double-Blind Method; Female; Furosemide; Glomerular Filtration Rate; Humans; Imidazoles; Kidney; Liver Cirrhosis; Male; Middle Aged; Prostaglandins F; Salicylates; Thromboxane B2; Time Factors

A double-blind crossover study versus placebo of the renal effects of the nonsteroidal anti-inflammatory drug imidazole 2-hydroxybenzoate was conducted in 10 patients with compensated liver cirrhosis. The administration of the drug (750 mg, t.i.d., for three days) did not affect renal plasma flow, glomerular filtration rate, free water clearance nor the urinary excretion of sodium or potassium. Values of plasma renin activity also did not change after drug administration. Direct tubular damage from imidazole 2-hydroxybenzoate was also excluded by normal excretion of beta-2-microglobulin and N-acetyl-beta-D-glucosaminidase. Urinary 6-keto-PGF1 alpha output were comparable during imidazole 2-hydroxybenzoate and placebo administration. These data indicate that this nonsteroidal antiinflammatory drug does not affect the renal function in patients with compensated liver cirrhosis.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Humans; Imidazoles; Kidney; Kidney Function Tests; Liver Cirrhosis; Male; Metabolic Clearance Rate; Middle Aged; p-Aminohippuric Acid; Pilot Projects; Renal Circulation; Salicylates

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 60-day double-blind parallel group clinical trial in 31 patients with osteoarthritis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, urinalysis and faecal occult blood was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and less severe in the group treated with imidazole salicylate.

Topics: Adult; Aged; Double-Blind Method; Female; Humans; Ibuprofen; Imidazoles; Knee Joint; Male; Middle Aged; Osteoarthritis; Osteoarthritis, Hip; Salicylates

The clinical efficacy and gastroduodenal tolerability of imidazole salicylate (imidazole 2-hydroxybenzoate, ITF 182), a new synthetic drug with an anti-inflammatory action, was evaluated endoscopically in comparison with those of piroxicam in elderly patients suffering from osteoarthrosis. Of the 41 patients entering the trial, only 38 completed the protocol (6 men and 32 women; mean age, 71; range, 65-80 years). After upper gastrointestinal endoscopy for the purpose of excluding gastric and duodenal mucosal lesions, the patients were allocated at random, according to a double-blind, double-dummy protocol, to treatment either with imidazole salicylate 750 mg three times daily or with piroxicam 20 mg once daily for a period of 4 weeks. Imidazole salicylate proved active in controlling a number of the pain symptoms caused by arthrosis, although its efficacy was inferior to that of piroxicam. Grade 2 gastric mucosal lesions were detected in 1 of 20 patients (5%) treated with imidazole salicylate; lesions corresponding to grades 2, 3, and 4 were found in 6 of 18 (33%) of those treated with piroxicam (P = .034). Painful dyspepsia was reported by 15% of the patients in the imidazole salicylate group and by 28% of those in the piroxicam group. On the basis of these results and under the experimental conditions adopted in this trial, the authors concluded that imidazole salicylate is characterized by good gastric tolerability and can thus be used in the treatment of rheumatic diseases in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Activities of Daily Living; Aged; Anti-Inflammatory Agents, Non-Steroidal; Consumer Behavior; Double-Blind Method; Endoscopy; Female; Humans; Imidazoles; Male; Osteoarthritis; Peptic Ulcer; Piroxicam; Salicylates

In order to evaluate the incidence of side-effects (S.E.), the withdrawal rate and the type of S.E. of the new antiinflammatory agent imidazole salicylate, we performed an analysis of 33 clinical trials involving 1408 patients treated with 750 mg t.i.d. (tablets or solution) or 1000 mg b.i.d. (granulated powder), taking into account all the factors (treatment duration, pharmaceutical form, indications, etc.) that could influence the type and incidence of S.E. Slight and transient episodes of pyrosis or epigastric pain represented the great majority of S.E. The overall rate of withdrawal was 1.8%. According to the duration of therapy, the incidence of S.E. was: 2-3 days, 3.3%; 5-7 days, 5.6%; 10-14 days, 8.8%; 30 days, 10.2%. The pharmaceutical forms, the treated pathologies and the various experimental designs adopted (double-blind, open, etc.) did not influence the S.E. rate. With imidazole salicylate the overall incidence of S.E. was always lower than other NSAID's ranging from 10% to 64% of that observed with the reference drugs (other salicylates, ibuprofen, naproxen, flurbiprofen, piroxicam, diclofenac). In conclusion, this analysis showed a linear relationship between S.E. and exposure time up to 10-12 days, followed by a clear trend toward a plateau of 10% of S.E. with treatments up to 30 days. Therefore the risk-benefit ratio, particularly when compared with that of the reference drugs, seems to be very favourable.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Humans; Imidazoles; Meta-Analysis as Topic; Salicylates

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.

Topics: Acetylglucosaminidase; Adolescent; Adult; Albuminuria; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Type 1; Female; Glycosaminoglycans; Humans; Imidazoles; Male; Middle Aged; Salicylates

In a 24-week multicenter double-blind clinical trial, efficacy and safety of the novel nonsteroidal anti-inflammatory drug imidazole salicylate (750 mg t.i.d. per os) and ibuprofen (600 mg t.i.d. per os) were compared in 60 patients with classical or definite rheumatoid arthritis, randomly assigned to one of the two treatment groups. The patients improved significantly with both treatments in all the clinical parameters examined such as the duration of morning stiffness, grip strength of both hands, Ritchie's articular index and severity of joint pain. The systemic tolerability, assessed by hematological, liver and kidney function tests was excellent with both treatments. The incidence of side effects was overall fairly low with both drugs, and lower in the group treated with imidazole salicylate (23% vs. 33%).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Ibuprofen; Imidazoles; Male; Middle Aged; Random Allocation; Salicylates

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 30-day multicenter double-blind clinical trial in patients with osteoarthrosis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and lower in the group treated with imidazole salicylate.

Topics: Adult; Aged; Anti-Inflammatory Agents; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Ibuprofen; Imidazoles; Male; Middle Aged; Osteoarthritis; Random Allocation; Salicylates

To evaluate whether imidazole salicylate, a recently developed NSAID, can interfere with the antihypertensive effect of atenolol and to compare its action with that of indomethacin, 9 essential hypertensives, while on prolonged (more than 1 month) treatment with atenolol (100 mg qd) received, according to a double-blind cross-over study, imidazole salicylate (750 mg t.i.d.) or indomethacin (50 mg b.i.d. plus a placebo tablet) for 1 week, reverting the treatment after a 2-week wash-out period. While indomethacin addition significantly increased blood pressure, when compared to atenolol alone, imidazole salicylate did not change it. These data show that imidazole salicylate, unlike indomethacin, does not reduce the antihypertensive effect of atenolol.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Atenolol; Blood Pressure; Drug Interactions; Evaluation Studies as Topic; Female; Humans; Hypertension; Imidazoles; Indomethacin; Male; Middle Aged; Random Allocation; Salicylates

The efficacy and safety of the nonsteroidal anti-inflammatory drugs imidazole.2-hydroxybenzoate and sulindac were compared in 30 patients with classical or definite rheumatoid arthritis. The trial was designed as a randomized parallel-group study comprising 15 patients given imidazole.2-hydroxybenzoate and 15 given sulindac orally for 28 days. Patients in both groups improved significantly in almost all of the variables evaluated. Imidazole.2-hydroxybenzoate was more effective than sulindac on Ritchie's articular index, left hand proximal interphalangeal joint circumference, erythrocyte sedimentation rate, and C-reactive protein. The incidence of side effects was significantly higher in patients treated with sulindac.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Clinical Trials as Topic; Female; Humans; Imidazoles; Indenes; Male; Middle Aged; Pain; Random Allocation; Salicylates; Sulindac

Topics: Aged; Anti-Inflammatory Agents; Clinical Trials as Topic; Diclofenac; Double-Blind Method; Female; Humans; Imidazoles; Male; Osteoarthritis; Random Allocation; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents; Clinical Trials as Topic; Double-Blind Method; Female; Feprazone; Humans; Imidazoles; Male; Middle Aged; Phenylbutazone; Random Allocation; Respiratory Tract Diseases; Salicylates

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Imidazoles; Joint Diseases; Male; Middle Aged; Pain; Random Allocation; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Double-Blind Method; Female; Fever; Humans; Imidazoles; Male; Middle Aged; Pain; Salicylates

Topics: Adolescent; Adult; Ampicillin; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Female; Humans; Imidazoles; Male; Middle Aged; Respiratory Tract Infections; Salicylates

Topics: Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Female; Fever; Humans; Imidazoles; Infant; Influenza, Human; Male; Rheumatic Diseases; Salicylates

The interactions of selezen (imidazole salicylate) with human blood components were studied by equilibrium dialysis. These interactions were limited to the binding of salicylate to human serum albumin (HSA). The binding was saturable and involved several classes of binding sites with different association constants. A competition study indicated that salicylic acid at high concentration was able to displace warfarin and digitoxin but not glibenclamide from their HSA sites. On the other hand, selezen serum binding was decreased in renal impaired patients and this result was probably linked to the decreases in HSA concentration. So the use of small dosage regimens of selezen to these patients can be proposed. The same recommendation may be done for cirrhotic patients, where the decrease of selezen binding percentage was observed and due to both hypoalbuminemia and hyperbilirubinemia.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Chronic Disease; Dialysis; Erythrocytes; Humans; Imidazoles; Kidney Failure, Chronic; Liver Diseases; Salicylates; Salicylic Acid

Topics: Adult; Albuminuria; Blood Glucose; Erythrocytes; Female; Humans; Imidazoles; Male; Middle Aged; Salicylates

Topics: Administration, Intravaginal; Adolescent; Adult; Female; Humans; Imidazoles; Middle Aged; Salicylates; Vaginitis

A postmarketing survey was conducted by 37 orthopedists and traumatologists among 700 patients of both sexes, aged 7 to 87 years, to evaluate the efficacy and tolerability of imidazole salicylate. The 467 patients with osteoarthrosis received 750-mg tablets (TID) for up to one month and 233 patients with traumatic pathologies received imidazole salicylate gel (BID-TID) for ten days, or tablets (BID-TID), or both gel and tablets combined. The treatment was satisfactory in both patient groups, significantly reducing the intensity of pain and swelling and improving articular function. No adverse experiences that had not been reported previously were recorded; only some gastrointestinal side effects exceeded an incidence of 1%.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Bone and Bones; Child; Female; Humans; Imidazoles; Male; Middle Aged; Muscles; Osteoarthritis; Product Surveillance, Postmarketing; Salicylates

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Captopril; Female; Humans; Hypertension; Imidazoles; Indomethacin; Male; Middle Aged; Salicylates; Time Factors

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Humans; Imidazoles; Male; Pipemidic Acid; Prostatitis; Random Allocation; Salicylates; Suppositories

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Drug Therapy, Combination; Drug Tolerance; Female; Glucosephosphate Dehydrogenase Deficiency; Humans; Imidazoles; Infant; Male; Salicylates; Time Factors

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child; Female; Humans; Imidazoles; Male; Salicylates

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Child; Female; Gingivitis; Humans; Imidazoles; Male; Middle Aged; Mouth Diseases; Periapical Abscess; Salicylates; Tooth Extraction

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Athletic Injuries; Child; Female; Humans; Imidazoles; Male; Salicylates

Imidazole 2-hydroxybenzoate is a novel nonsteroidal antiinflammatory agent which clinico-pharmacologically and pharmacokinetically has to be understood as imidazole and salicylic acid. The pharmacokinetic profile of both components after single and multiple oral (tablets, drops), and topical administration (gel 5%)--the latter in a pilot study--was evaluated as well as protein-binding, relative bioavailability and the metabolic pattern. Absorption and elimination of the two compounds were fast. All essential pharmacokinetic and bioavailability parameters seem to be in a good agreement with data published in the literature and an accumulation tendency was not observed. The t1/2 beta for imidazole (oral administration) was determined for a single dose at 2.98 +/- 1.13 h, for a multiple dose (last dose) at 1.86 +/- 0.78 h; for salicylic acid the t1/2 beta for a single dose was determined at 6.46 +/- 3.79 h and for a multiple dose (last dose) at 6.40 +/- 3.36 h. The protein-binding of imidazole was in the range of 5-15% and of salicylic acid of about 80-85%. The relative bioavailability was calculated for imidazole (single dose) at 138% and for multiple dosing (last dose) at 113%; for salicylic acid the values for single dose were 148% and for multiple dosing (last dose) 128%. The tolerability was altogether good and no adverse reactions could be observed. The topical administration (pilot study) with gel 5% did not show any systemic effects or adverse reactions. The local tolerability was very good. Statistically, there were only slight differences between tablets and drops overall since only one p-value was less than 0.01. According to the small sum of squared residuals, the NONLIN-program performed an excellent fitting of the data to the model equation.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Chromatography, High Pressure Liquid; Humans; Imidazoles; Kinetics; Male; Models, Biological; Protein Binding; Salicylates; Serum Albumin; Solutions; Tablets

The effects of drugs on the production of superoxide anion from neutrophils stimulated by N-formylmethionyl-leucyl-phenylalanine (FMLP) were examined. Drugs acting on specific receptors, such as beta-adrenergic agonists (e.g. fenoterol, salbutamol) inhibited FMLP-evoked superoxide in a dose-dependent fashion. The order of activity: isoprenaline greater than fenoterol greater than salbutamol is the same as that found by assaying their effects on lysosomal enzyme release. Superoxide production from human neutrophils can also be affected in different manners, such as by a scavenging mechanism. A new non-steroidal anti-inflammatory drug, imidazole 2-hydroxybenzoate, by forming complexes with copper, displayed a significant superoxide dismutase activity which would contribute to explain its anti-inflammatory effect in vivo.

Topics: Adrenergic beta-Agonists; Albuterol; Fenoterol; Humans; Imidazoles; In Vitro Techniques; Isoproterenol; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Salicylates; Superoxides

Topics: Adult; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Muscles; Pain; Pindolol; Salicylates; Wounds and Injuries

Topics: Adolescent; Adult; Aged; Aminopyrine; Anti-Inflammatory Agents; Bone and Bones; Child; Dipyrone; Female; Humans; Imidazoles; Male; Middle Aged; Pain, Postoperative; Pyrazolones; Salicylates

Topics: Anti-Inflammatory Agents; Humans; Imidazoles; Salicylates

Topics: Anti-Inflammatory Agents; Humans; Imidazoles; Inflammation; Prostaglandins; Salicylates

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Female; Genital Diseases, Female; Humans; Imidazoles; Middle Aged; Naproxen; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Oxyphenbutazone; Salicylates; Urologic Diseases

Topics: Adult; Aged; Anti-Inflammatory Agents; Arthritis; Female; Hip Joint; Humans; Imidazoles; Male; Middle Aged; Piroxicam; Salicylates; Spinal Diseases; Thiazines

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Imidazoles; Male; Middle Aged; Naproxen; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Osteoarthritis; Pain; Salicylates

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Child, Preschool; Female; Humans; Imidazoles; Infant; Male; Respiratory Tract Diseases; Salicylates

Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Child, Preschool; Female; Fever; Humans; Imidazoles; Infant; Male; Respiratory Tract Infections; Salicylates

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Female; Fever; Humans; Imidazoles; Infant; Male; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Peptide Hydrolases; Respiratory Tract Diseases; Salicylates

Imidazole 2-hydroxybenzoate is a new antiphlogistic compound with analgesic and antipyretic properties undergoing clinical investigations. The purpose of this pilot study was to evaluate new methods for the quantitation of imidazole, salicylic acid and salicyluric acid in plasma and urine. Imidazole metabolites caused considerable methodologic difficulties in plasma and urine. They were below the detectable limit. Salicylic acid metabolites were present in plasma also under the limit of detection (0.5 microgram/ml). In urine the metabolite salicyluric acid was measured in considerable quantities, whereas gentisinic acid was under the limit of detection. Three healthy volunteers were given a single p.o. dose of 750 mg imidazole 2-hydroxybenzoate in order to examine the practicability of these new methods a well as to evaluate the pharmacokinetics. The data are presented and interpreted. Further studies in this respect are advised.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Biotransformation; Chromatography, High Pressure Liquid; Hippurates; Humans; Imidazoles; Kinetics; Models, Biological; Pilot Projects; Salicylates; Salicylic Acid

The behavior of imidazole 2-hydroxybenzoate (ITF 182), acetylsalicylic acid (ASA) and indometacin (INN; in some pharmacopoeias called indomethacin) in inhibiting thromboxane A2 (TXA2) and prostaglandin (PGs) production in the blood of the rat intravenously injected with arachidonic acid was studied. ITF 182 caused a selective inhibition of TXA2 production with a time-dependent reversible action. An irreversible inhibition of PGs production was shown by ASA whereas a reversible inhibition could be observed with indometacin. The PGs involved in the physiological processes, may be spared after ITF 182 administration contrary to what occurs after ASA or indometacin administration.

Topics: Animals; Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Aspirin; Cyclooxygenase Inhibitors; Imidazoles; Indomethacin; Injections, Intravenous; Male; Prostaglandins; Rats; Rats, Inbred Strains; Salicylates; Thromboxane A2; Thromboxane-A Synthase; Thromboxanes

The penetration of the two components of imidazole 2-hydroxybenzoate (ITF 182), imidazole and salicylate, into inflamed sites induced by intrapleural injection of carrageenin in the rat and by a urate-cotton pellet implantation in the knee joint of the rabbit is studied. The results obtained show that the two components of the salt penetrate rapidly the inflamed sites and display different kinetic profiles: imidazole diffuses throughout inflamed and non-inflamed fluids without any specific localization, salicylate shows preferential localization in inflamed fluids and remains longer than imidazole.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Carrageenan; Exudates and Transudates; Imidazoles; Inflammation; Knee Joint; Male; Pleura; Pleurisy; Rabbits; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Synovial Membrane

Superfused rings of rabbit basilar arteries are more sensitive than those of saphenous arteries to the contractions induced by a prostaglandin endoperoxide analogue (U-46 619) and by a thromboxane A2 (TXA2) generating system. 5-Hydroxytryptamine aggravates the latter. Prostaglandin I2 (PGI2) on the other hand, relaxes only the basilar rings without affecting the saphenous. Imidazole 2-hydroxybenzoate (ITF 182), at doses that do not interfere with platelet cyclooxygenase, reduces the contractions induced by the TXA2 generating system on both arteries because it reduces the platelet TXA2 synthetase enzyme. TXA2 is involved in the aetiology of strokes and cerebral vasospasms while PGI2 plays a physiological role in the maintenance of cerebral arterial tone. The high sensitivity of cerebral arteries to contractures caused by TXA2 together with the ability of ITF 182 to reduce them by inhibiting TXA2 production and to spare physiological PG production suggest a beneficial effect of the drug in cerebral vasospasms.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Anti-Inflammatory Agents; Arteries; Basilar Artery; Dinoprostone; Imidazoles; In Vitro Techniques; Leg; Male; Muscle Contraction; Muscle, Smooth, Vascular; Prostaglandin Endoperoxides, Synthetic; Prostaglandins E; Rabbits; Salicylates; Thromboxane A2; Thromboxanes

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Central Nervous System; Death, Sudden; Imidazoles; In Vitro Techniques; Kinetics; Male; Mice; Platelet Aggregation; Rabbits; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid; Stomach Ulcer; Thromboxane A2; Thromboxanes