pyrimidinones and Stomach-Ulcer

Dihydropyrimidinone derivatives containing piperidine moiety were synthesised in a good yield. All the compounds were confirmed by elemental analysis and spectral data. Anti-ulcer activity of novel dihydropyrimidinone-piperidine hybrids (1-18) was evaluated. Among them, four compounds (3, 8, 11 and 15) were found to be most active in 80% ethanol-induced ulcer experimental animal model. All the potent compounds were further evaluated for anti-ulcer activity by different in vivo anti-ulcer models to study the effect of compounds on anti-secretory and cytoprotective activities. All the active compounds inhibited the formation of gastric ulcers and increased the formation of gastric mucin secretion. Compound 15 was found to be the most potent compound of the series as anti-ulcer agent. Additional experimental studies on lead compound 15 will result in a new class of orally active molecule for anti-ulcer activity.

Topics: Animals; Anti-Ulcer Agents; Crystallography, X-Ray; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Models, Molecular; Molecular Structure; Piperidines; Pyrimidinones; Rats; Rats, Wistar; Stomach Ulcer; Structure-Activity Relationship

Twelve new 4-(1H-indol-3-yl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-2-ones/thiones (7-18) have been synthesized by reacting 1-aryl-3-(1H-indol-3-yl)-2-propen-1-one with urea and thiourea in ethanolic potassium hydroxide. Their structures have been confirmed by IR, 1H NMR and mass spectral data. The compounds were tested for their anti-inflammatory activity. Test results revealed that compounds showed 49.5 to 70.7% anti-inflammatory activity where-as the standard drug ibuprofen showed 86.4% activity at the same oral dose. Four compounds, 4-(1H-indol-3-yl)-6-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-2-one (8), 4-(1H-indol-3-yl)-6-(4-methylphenyl)-1,2,3,4-tetrahydropyrimidin-2-one (10), 4-(1H-indol-3-yl)-6-(4-chlorophenyl)-1,2,3,4-tetrahydropyrimidin-2-thione (14), 4-(1H-indol-3-yl)-6-(4-methylphenyl)-1,2,3,4-tetrahydropyrimidin-2-thione (16), that showed significant anti-inflammatory activity were selected to study their ulcerogenic and lipid peroxidation activities. All tested compounds showed significant reduction in the ulcerogenic potential and lipid peroxidation compared to the standard drug ibuprofen.

Topics: Animals; Anti-Inflammatory Agents; Female; Male; Pyrimidinones; Rats; Stomach Ulcer; Structure-Activity Relationship; Thiones

A new series of 2-mercapto-3-substituted-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-ones were synthesised by reacting 3-amino-2-mercapto-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one with different aldehydes and ketones. The starting material 3-amino-2-mercapto-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one was synthesised from 2-amino-3-carbethoxy-4,5-dimethyl thiophene by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, among these compound AS1 showed more potent analgesic and anti-inflammatory activities and the compound AS3 showed equipotent analgesic and anti-inflammatory activities when compared to the reference standard diclofenac sodium.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Pain Measurement; Pyrimidinones; Rats; Rats, Wistar; Stomach Ulcer; Structure-Activity Relationship; Sulfhydryl Compounds; Thiophenes

In the present work, design, synthesis, and pharmacological evaluation of the analgesic, anti-inflammatory, and ulcerogenic-index activities of new 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones, structurally planed by exploiting a clear concept of bio-isosterism, are reported. All compounds exhibited significant analgesic and anti-inflammatory activity. Compounds A1, A3 showed higher analgesic activity and more potent anti-inflammatory activity than that of the reference compound diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to that of acetylsalicylic acid.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Magnetic Resonance Spectroscopy; Male; Pain Measurement; Pyrimidinones; Rats; Rats, Wistar; Stomach Ulcer; Structure-Activity Relationship; Sulfones; Thiophenes

A variety of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-4(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)dithiocarbamic acid methyl ester (5) with a variety of amines. The starting material dithiocarbamate (5) was synthesized from 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzo (b) thiophene (1) by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory, ulcerogenicity index and antibacterial activities. While the test compounds exhibited significant activity, the compounds 1-methyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A1), 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A4) showed more potent analgesic activity and the compounds 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno-[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d] pyrimidin-3-yl)thiourea (A4) showed more potent anti-inflammatory activity than the reference standard diclofenac sodium.

Topics: Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Microbial Sensitivity Tests; Pyrimidinones; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer

The synthesis, the analgesic and anti-inflammatory activities of two series of phenyl derivatives containing 5,6-dimethyl-thieno[2,3-d]pyrimidin-4(1H)-one and 4H-pyrimido[5,4-b]indol-4-one system, respectively, are reported. Two of these derivatives, 6A and 9B, showed interesting activities. The results of the pharmacological assays are discussed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Edema; Guinea Pigs; Indicators and Reagents; Indoles; Male; Pain Measurement; Peritonitis; Pyrimidines; Pyrimidinones; Rats; Rats, Sprague-Dawley; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer

New thiadiazolothienopyrimidinones were synthesized in continuation of efforts to prepare thienopyrimidine derivatives with analgesic and antiinflammatory activities. In this study, the effect of various substituents in the thiophene ring on the pharmacological activity of the compounds was investigated.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemical Phenomena; Chemistry, Physical; Edema; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mice; Pain Measurement; Peritonitis; Pyrimidinones; Rats; Spectrophotometry, Infrared; Stomach Ulcer; Thiazoles

A series of new 1,3-disubstituted thieno[1,3-d]pyrimidine-2,4(1H,3H)-diones were prepared to investigate their analgesic and anti-inflammatory properties. The analgesic and anti-inflammatory activities of synthesized compounds were investigated by the phenylquinone-induced writhing syndrome test, carrageenan rat paw oedema test and acetic acid-induced peritonitis assay. Most of the new compounds were found to be superior to mefenamic acid, as they were devoid of any ulcerogenic activity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Chemical Phenomena; Chemistry, Physical; Inflammation; Lethal Dose 50; Mice; Pain Measurement; Pyrimidinones; Rats; Stomach Ulcer

The effects of IGN-2098 on the healing process of acetic acid-induced gastric ulcer was investigated in comparison with the other histamine H2-receptor antagonists, famotidine and roxatidine acetate HCl, in rats. Ulcer was induced by the injection of acetic acid solution (20%, 0.05 ml). From the 4th day to 17th day after the ulcer induction, drugs were orally administered twice a day. On the 18th day after the ulcer induction, rats were sacrificed to measure the ulcer index macroscopically and to take pictures of the stomachs. Judging from the photographs, the prominence of ulcer the edge was graded into 4 classes, which showed a significant correlation with the histological amount of connective tissue at the ulcer edge. All drugs accelerated the healing of the ulcer, and the effect of IGN-2098 was the most remarkable. In addition, IGN-2098-treatment exhibited more marked inhibition against the prominence of the ulcer edge as compared with the control group. Based on these results, it is concluded that IGN-2098 may be a useful drug for the clinical treatment of ulcer and that the healing acceleration by IGN-2098 without prominence of the ulcer edge may induce no relapse of the ulcer after healing.

Topics: Acetates; Acetic Acid; Animals; Anti-Ulcer Agents; Famotidine; Histamine H2 Antagonists; Male; Piperidines; Pyrimidinones; Rats; Rats, Sprague-Dawley; Stomach Ulcer

Two series of novel derivatives based on the thienopyrimidine and pyrimidoindole ring systems, both N-substituted in position 3, have been synthesized. The compounds were obtained by reaction of N-amino groups of 5,6-dimethyl-thieno[2,3-d]pyrimidin-2,4-dione and of 5H-pyrimido[5,4-b]indol-2,4-dione with aromatic aldehydes. Some of these substances showed an appreciable analgesic activity, a good antiinflammatory activity, a low acute toxicity with an optimal gastric tolerance.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bacteria; Behavior, Animal; Carrageenan; Deuterium; Fungi; Indoles; Inflammation; Magnetic Resonance Spectroscopy; Male; Mice; Microbial Sensitivity Tests; Pain Measurement; Peritonitis; Pyrimidinones; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Thiophenes

The cytoprotective effect of different types of 4h-pyrido[1,2-a]pyrimidin-4-one derivatives was investigated. Short synthesis of the investigated compounds was depicted. The gastroprotective effect was determined against acidified ethanol induced mucosal lesions in rats. The most effective compounds belong to unsaturated 4-oxo-4h-pyrido[1,2-a]pyrimidine-3-carboxamide derivatives, and the most active one contains a methyl group in position 6 and a cyclopentyl group on the nitrogen of the carboxamide group. Further pharmacological, biochemical and clinical studies may justify, that the representative of this type of compounds may be useful as prophylactic agents against gastric damage caused by non-steroidal antiinflammatory agents.

Topics: Animals; Anti-Ulcer Agents; Atropine; Cimetidine; Decision Trees; Ethanol; Indomethacin; Pyrimidinones; Rats; Stomach Ulcer; Structure-Activity Relationship

According earlier, investigations nitrogen bridgehead compounds make a representative group of non-prostaglandin type gastroprotective agents. One member of this group is CHINOIN-127 (1,6-dimethyl-4-oxo-1, 6, 7, 8, 9, 9a-hexahydro-4H-pyrido-(1, 2a)-pyrimidine-3-carbox-amide). CHINOIN-127 is a potent non-narcotic analgesic and antiinflammatory agent and has a remarkable protective effect on indomethacin induced ulcer (ED50 = 25 mg/kg p.o.) and on acidified ethanol induced ulcer (ED50 = 26 mg/kg p.o.). In this study we examined the mechanism of action of cytoprotective effect of this drug and we made a comparison between the cytoprotective effect of 20% ethanol and 25 mg/kg CHINOIN-127. In the gastric mucosa of control rats we observed a balance between TxA2 and PGI2 (PGI2/TxA2 = 3.8) and between the cytoprotective prostaglandins (PGI2 and PGE2) and ulcerogen eicosanoids (TxA2 and leukotrienes) (PGI2 + PGE2/TxA2 + LTs = 3.9). 100% ethanol treatment causes disintegration of this balance, shifting the synthesis towards the ulcerogen eicosanoids production. CHINOIN-127 and 20% ethanol pretreatment improves the deranged balance between cytoprotective prostaglandins and ulcerogen eicosanoids. Our results demonstrate that CHINOIN-127 and 20% ethanol have a similar mechanism of cytoprotective action on ethanol induced ulcer in rats.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Epoprostenol; Ethanol; Gastric Mucosa; Pyrimidinones; Rats; Rats, Wistar; Stomach Ulcer; Thromboxane B2

A new compound, IGN-2098 [5,6-dimethyl-2-[4-<3-(1-piperidinomethyl) phenoxy>cis-butenylamino]-4-(1H)-pyrimidone.2HCl], was found to be a potential histamine H2-receptor antagonist in the guinea pig atrium. IGN-2098, given p.o., significantly and persistently (for more than 12 hr) inhibited the basal gastric secretion in pylorus-ligated rats. The agent also significantly inhibited the basal gastric secretion when given by the s.c.-, i.d.- or i.p.-route. Stimulated gastric secretion in fistula rats in response to histamine, carbachol or pentagastrin was also significantly inhibited with IGN-2098 given s.c. Pretreatment with IGN-2098 (p.o.) significantly protected the gastric mucosa against pylorus ligation-, water-immersion stress-, histamine-, indomethacin-, HCl.aspirin-, and HCl.ethanol-induced gastric lesions. In addition, the agent significantly protected the duodenal mucosa against mepirizole-induced ulcers. Based upon the ED50 values, the antisecretory effects on histamine, carbachol or pentagastrin-stimulated acid secretion were 6.0, 37.0 or 80 times more potent than roxatidine, respectively. As to the anti-lesion effects on HCl.aspirin-induced gastric lesions or mepirizole-induced duodenal ulcers, IGN-2098 was 8.1 or 14.8 times more potent than roxatidine, respectively. These results suggest that IGN-2098 will be a useful drug for the treatment of gastric and duodenal lesions in man.

Topics: Animals; Anti-Ulcer Agents; Dose-Response Relationship, Drug; Duodenal Ulcer; Gastric Juice; Histamine H2 Antagonists; Male; Piperidines; Pyrimidinones; Rats; Rats, Inbred Strains; Stomach Ulcer

Topics: Animals; Anti-Ulcer Agents; Epoprostenol; Indomethacin; Prostaglandin-Endoperoxide Synthases; Pyrimidinones; Rats; Stomach Ulcer; Thromboxane-A Synthase

A study was carried out to evaluate the effect of cysteamine-HCl administration on gizzard ulceration and growth performance in broiler chicks. The effectiveness of the histamine H2-receptor antagonist, SKF 93479, in preventing gizzard ulcerations when given in combination with cysteamine-HCl was also examined. In the initial experiment cysteamine-HCl at the level of 2400 mg/kg of the diet caused severe gizzard ulceration and mortality and decreased feed intake and growth in chicks. The effect was not seen when cysteamine-HCl was administered at 600 or 1200 mg/kg of the diet. In Experiment 2 broiler chicks administered cysteamine-HCl at 1800 mg/kg of the diet had an increased incidence of gizzard ulceration and decreased growth performance. The severity of gizzard lesions and the depression of growth performance were not as great as in the group in Experiment 1 which received the 2400 mg/kg level of cysteamine-HCl. Addition of the H2 antagonist SKF 93479 at 54 mg/kg of the diet had no effect on improving gizzard ulcer score or growth performance in chicks which received cysteamine-HCl at the 1800 mg/kg of the diet level. From these data it appears that the administration of ulcerogenic levels of cysteamine-HCl in the chicken may involve a more complex pathogenesis in which factors other than acid hypersecretion are involved.

Topics: Animals; Body Weight; Chickens; Cysteamine; Drug Combinations; Gizzard, Avian; Histamine H2 Antagonists; Male; Poultry Diseases; Pyrimidinones; Stomach Ulcer

1,6-Dimethyl-3-carbethoxy-4-oxo-6,7,8,9-tetrahydro-homopyrimidazol (rimazolium, MZ-144) proved to be effective in all the analgesic assays used (independently of the nociceptive stimulus applied) (hot plate, tail flick, writhing tests, Randall-Selitto test, tail clip, surgical pain) differing in this respect from the nonsteroidal antiinflammatory analgetics. The analgesic, antiinflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared. The prostaglandin (PG) mediated pain (acetylcholine-, adenosine triphosphate- and acetic acid-induced writhing) was inhibited by all the three types of compounds, however, pain reaction where PGs are not involved (MgSO4-writhing) was inhibited only by rimazolium and morphine but not, or only slightly, by PG synthesis inhibitors. While the analgesic effect of rimazolium alone was not reversed by naloxone, the full analgesia evoked by the ineffective doses of morphine and rimazolium combinations was completely naloxone reversible (pA2 = 8.6). In addition, rimazolium produced weak analgesia by intrathecal administration, and its concomitant s.c. administration enhanced the analgesic effect of intrathecally administered morphine. Furthermore, chronic treatment with rimazolium failed to influence its analgesic activity, and no tolerance developed and no naloxone precipitated withdrawal syndrome could be seen. In addition, rimazolium did not substitute for morphine in morphine dependent rats, after morphine withdrawal, thus indicating that rimazolium lacks the capacity of producing opiate-like physiological dependence. Also rimazolium fails to show any indication of narcotic-like abuse liability by any of clinical assessments. Rimazolium, morphine and indometacin inhibited the carrageenin-induced edema formation. Gastrointestinal lesions produced by indometacin were depressed by rimazolium and enhanced by morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cats; Dogs; Drug Tolerance; Guinea Pigs; Indomethacin; Macaca mulatta; Male; Mice; Pyrimidinones; Rabbits; Rats; Reaction Time; Stomach Ulcer; Substance Withdrawal Syndrome; Substance-Related Disorders

The antipyretic, analgesic, antinflammatory and antiulcerogenic properties of a new compound 1,4 dihydro-1-ethyl-7-phenylpyrrol (1,2-a)-pyrimidine-4-one (V33) are described. V33 on a mg/kg basis possesses antipyretic and analgesic properties at doses lower than paracetamol and which do not produce hypothermia or motor impairment. V33 possesses antiinflammatory activity and decreases the production of LTB4 from inflammatory exudates without affecting PGE2 content. V33 is not only devoid of gastric ulcerogenic properties but exerts antiulcer activity toward various ulcerogenic stimuli. Lethal dose 50% (LD50) of V33 is higher that of paracetamol.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoquinones; Dose-Response Relationship, Drug; Fever; Humans; In Vitro Techniques; Leukotriene B4; Male; Mice; Oxygen Consumption; Pyrimidinones; Quinones; Rats; Rats, Inbred Strains; Reaction Time; Stomach Ulcer

A series of (E)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo-[1,5-a]pyrimidine-7-ones were synthesized and evaluated for the inhibition of stress-induced gastric ulcers in the rat after oral administration. Several molecules were found to be very active. The particularly interesting compound (E)-1-(3-chlorophenyl)-5-[2-(3-pyridyl)ethenyl]-1H,7H-pyrazolo[1,5-a]- pyrimidine-7-one was chosen for wider pharmacological investigation.

Topics: Animals; Anti-Ulcer Agents; Chemical Phenomena; Chemistry; Gastric Juice; Male; Parasympatholytics; Pyrazoles; Pyrimidinones; Rats; Rats, Inbred Strains; Stomach Ulcer; Stress, Psychological

Four experiments were conducted to evaluate the effect of diet and the administration of H2-antagonists in feed on gastric ulcer formation and performance of growing-finishing swine. Pigs receiving a finely ground diet (less than lmm) grew faster (.73 vs .68 kg/d, P less than .01) and had better feed utilization (3.47 vs 3.76, P less than .01) than pigs receiving a cracked corn-based diet. Incidence of ulcers in the esophageal region of the stomach of pigs fed the finely ground diet was greater (P less than .01) than in pigs fed cracked corn. The average daily gain of pigs receiving the finely ground diet was inversely related to ulcer incidence (r = .403, P less than .01, df = 59). The addition of 5, 10, 20 or 100 ppm of the H2-antagonist, metiamide, or 6, 18 or 54 ppm of SK&F 93479 to the finely ground diet did not improve pig performance or affect the incidence of gastric ulceration. The addition of 2, 6 and 18 ppm of SK&F 93479 to a corn-soy diet containing 4.5% alfalfa meal caused a reduction in gastric ulceration (P less than .05) and improved feed utilization by 3.2% (P less than .05). These data suggest that finely ground diets improve the performance of growing-finishing swine, but increase the incidence of ulcers in the esophageal region of the stomach. Severe gastric ulceration adversely affects swine performance. Feeding H2-antagonists does not reduce the ulcerogenic properties of finely ground diets, suggesting factors other than gastric acid secretion are involved in ulcerogenesis. The use of H2-antagonists in corn-soy diets improves feed utilization and reduces ulceration.

Topics: Animal Feed; Animals; Disease Models, Animal; Female; Food Additives; Histamine H2 Antagonists; Male; Metiamide; Particle Size; Pyrimidinones; Stomach Ulcer; Swine; Swine Diseases; Thiourea

The analgesic, anti-inflammatory and gastrointestinal effects of rimazolium, morphine and prostaglandin synthesis inhibitors were compared in a battery of tests. Rimazolium, morphine and indomethacin all inhibited carrageenin-induced inflammation; however, the onset of action was different. The first (histamine-serotonin) phase was inhibited by rimazolium, the second (kinin) phase by morphine and the third (prostaglandin) by indomethacin. The chemoluminescence of leucocytes was inhibited by morphine and indomethacin but was unaffected by rimazolium. Prostaglandin-mediated pain (ACh, ATP, acetic acid writhing) was inhibited by all three types of compound; however, pain reaction where prostaglandins (PGs) are not involved (MgSO4 writhing) was inhibited by rimazolium and morphine, but not (or only slightly) by PG synthesis inhibitors. Gastric lesions produced by indomethacin were depressed by rimazolium and aggravated by morphine. These results suggest different mechanisms of anti-inflammatory and analgesic action of rimazolium, morphine and PG synthesis inhibitors.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Indomethacin; Leukocytes; Luminescent Measurements; Male; Morphine; Naloxone; Pyrimidinones; Rats; Rats, Inbred Strains; Stomach Ulcer

A series of 3-substituted pyridothienopyrimidin-4(3H)-ones has been synthesized from 2,7,9-trimethyl-4H-pyrido[3',2':4,5]thieno-[3,2-d] [ 1,3]oxazin-4-one. These compounds have been evaluated for analgesic, anti-inflammatory and antipyretic activities. The ulcerogenic effect of the compounds has been also studied.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Chemical Phenomena; Chemistry; Female; Male; Mice; Motor Activity; Pyrimidinones; Rats; Rats, Inbred Strains; Reaction Time; Stomach Ulcer

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidine-3-carbamide (Chinoin 127), a non-narcotic analgesic with potent antiinflammatory activity is described. Chinoin-127 is more potent as an analgesic in the hot plate, Randall-Selitto and writhing tests than is acetylsalicylic acid (ASA) and an effective antiphlogistic agent in a battery of tests (carrageenin, kaolin and dextran induced rat paw edema, Northover test, carrageenin induced abscess, implanted cotton pellet method, adjuvant arthritis) used for measuring antiinflammatory activity. The PG-synthesis inhibitors (indometacin, suprofen) were found to be devoid of analgesic activity, and great test-dependent variations in their antiinflammatory effect were observed. They proved to be inactive in the Northover test. Unusual grade of inhibition in the carrageenin-induced rat paw edema test was obtainable by the simultaneous administration of Chinoin 127 and indometacin.

Topics: Abscess; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Capillary Permeability; Carrageenan; Dextrans; Edema; Female; Granuloma; Kaolin; Male; Mice; Prostaglandins; Pyrimidinones; Rats; Stomach Ulcer