Antiinflammatory actions of ephedrines in acute inflammations1

Ephedrine (EP), pseudoephedrine (PEP), ephedroxane (EX) and pseudoephedroxane (PEX) inhibited carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice. Hind-paw edema induced by histamine, serotonin, bradykinin and prostaglandin E (1) was suppressed by these alkaloids, showing that they exert the antiinflammatory activity at the early exudative stage of inflammation. Although tolazoline and propranolol had no effects on the inhibitory activity of EX and PEX, treatment with tolazoline decreased the antiinflammatory activity of EP and PEP on carrageenin-induced hind-paw edema. Antiinflammatory activity of PEP was reduced by previous treatment with reserpine, indicating the antiinflammatory activity of EP and PEP to be partly concerned with the sympathetic nervous system. Although these alkaloids injected I.C.V. elicited no antiinflammatory actions on carrageenin-induced hind-paw edema and the inhibitory activity of morphine on carrageenin-induced hind-paw edema was potentiated by the concurrent administration of PEP and EX, demonstrating that the mechanism of antiinflammatory activity does not involve the central nervous system. Further, these alkaloids inhibited prostaglandin E (2) biosynthesis.     

Effect of the new antiallergic drug 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid on inflammatory reactions and platelet aggregation

A new chemical compound, 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), known to have antiallergic activity was investigated with respect to its antiinflammatory effect. Sm 857 did not inhibit ultraviolet-induced erythema in guinea pigs, intradermal increased vascular permeability induced by histamine in rats and carrageenin-induced edema of the rat hind paw. Further, the compound showed no influence on wound healing in rats and was observed to exert neither analgesic nor inhibitory effect on platelet aggregation. Sm 857 was thus found to have no effect at all on acute and chronic inflammatory reactions. It was denied, therefore, that any antiinflammatory effect might be involved in the antiallergic effect of Sm 857 but it may be related to an inhibitory effect on the release of mediators or on some earlier stage. Therefore investigation was carried out into its inhibitory action on dextran- and compound 48/80-induced edema of the rat hind paw. As a result, Sm 857 showed a stronger inhibitory effect on dextran edema than tranilast. Sm 857 inhibited endotoxin-induced diarrhea in mice and the effect was similar to that of tranilast, suggesting its inhibitory action on the release of mediators.     

美洛昔康抗炎作用的实验研究

目的观察美洛昔康的抗炎作用。方法采用大鼠急性、亚急性及免疫性炎症模型,观察美洛昔康对角叉菜胶致大鼠足跖肿胀和大鼠棉球肉芽肿的影响以及美洛昔康对大鼠佐剂性关节炎的预防和治疗作用。结果美洛昔康对多种致炎剂引起的炎性水肿均具有明显的抑制作用,1.0和3.0mg     

2-(E)-苯亚甲基-5-(N-取代胺甲基)环戊酮的合成及抗炎作用

本文报道19个2-(E)-苯亚甲基环戊酮Mannich碱类化合物的合成。所有产物结构经元素分析、核磁共振氢谱和红外光谱证实。初步药理试验表明部分化合物有较强的抗炎活性。其中1个化合物对二甲苯致小鼠耳廓肿胀、角叉菜胶致大鼠足爪肿胀和乙酸致小鼠腹腔毛细血管通透性增加均有显著的抑制作用,抑制能力与布洛芬、阿斯匹林相近。     

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 1st communication: inhibitory effects of rat paw edema

In the development process of a new nonsteroidal antiinflammatory drug (NSAID) with less toxicity and side-effects, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepein-2-yl) propionic acid (CN-100) was chosen as the most excellent NSAID from synthetic tricyclic compounds after screening test. For the series of studies on antiinflammatory effects of this compound in detail, its effect on rat paw edema induced by various phlogists was first investigated. The inhibitory effect of CN-100 on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. The effect was not affected by continuous administration for 2 weeks or adrenalectomy. Similarly to indometacin, CN-100 had no significant effect on yeast-induced edema mediated by 5-hydroxytryptamine and concanavalin-A-induced edema unrelated with prostaglandins. However, CN-100 displayed a weaker inhibitory effect on nystatin-induced edema than indometacin, suggesting that CN-100 has a low membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. CN-100 inhibited the sustained edema induced by mustard, but the drug did not interfere with the increase in body weight of rats. Indometacin in the same dose caused decrease in body weight and death. The toxicity of CN-100 was definitely less than that of indometacin, although both drugs were similar in antiinflammatory activity and mode of action on rat paw edema. Results suggest that CN-100 is an effective drug on not only acute but also subacute and chronic inflammation.     

Antinociceptive,antipyretic, and anti-inflammatory activities of <Emphasis Type="Italic">Putranjiva roxburghii</Emphasis> Wall. leaf extract in experimental animals

The effects of the ether extract from the leaves of Putranjiva roxburghii (P. roxburghii) Wall. were assessed on nociceptive responses in mice by using writhing, hot plate, and formalin tests and the antipyretic activity was determined in yeast-induced fever in rats. Anti-inflammatory activities were also investigated using carrageenin-induced paw edema in rats and croton oil-induced ear and anus edemas. The ether extract (100, 200, and 400 mg/kg, p.o.) of P. roxburghii dose-dependently produced analgesic activity in acetic acid-induced writhing in mice. The extract had no significant effect in the hot plate test in mice. At the dose of 400 mg/kg, the extract significantly suppressed the licking activity in the late phase of the formalin test in mice and decreased fever induced by yeast in rats. The extract exhibited moderate inhibitory activity of inflammation in carrageenin-induced paw edema in rats. The extract inhibited croton oil-induced ear edema in a dose-dependent manner (1.25, 2.5, and 5.0 mg/ear) in mice. The extract decreased anus edema induced by croton oil at the high dose of 800 mg/kg in rats. The results indicated that the ether extract of P. roxburghii leaves possesses analgesic, antipyretic, and anti-inflammatory activities.     

The antiinflammatory effect of EB-382

This study was conducted to clarify the antiinflammatory profile of EB-382, comparing it with those of ibuprofen and other antiinflammatory agents. EB-382 had a more potent inhibition on the acetic acid-induced intensive mouse intraperitoneal vascular permeability and carrageenin-induced rat hind paw edema, but a less potent inhibition on the ultraviolet-induced guinea-pig erythema and the prostaglandin biosynthesis in vitro than ibuprofen. The inhibition by EB-382 was equipotent to that of indomethacin on carrageenin-induced rat pleurisy and the zymosan air pouch, and it demonstrated a strong inhibition on the kallikrein and zymosan-induced intensive guinea-pig skin vascular permeability. EB-382 had a more effective activity on paper disk-induced granuloma and adjuvant arthritis, and it had a less potent action on the gastric mucosal membrane than ibuprofen. EB-382 had a weak action on histamine-induced rat back skin vascular permeability and heat-induced protein denaturation and hemolysis in vitro, as also shown by other test agents. The above results indicate that EB-382 will be useful as an antiinflammatory agent with a new pharmacological effectiveness besides possessing properties common to other acidic non-steroidal antiinflammatory agents in clinical studies.     

Pharmacological studies on leaf of Arctostaphylos uva-ursi (L.) Spreng. V. Effect of water extract from Arctostaphylos uva-ursi (L.) Spreng. (bearberry leaf) on the antiallergic and antiinflammatory activities of dexamethasone ointment]

Effects of water extract (UW-ext) from the leaf of Arctostaphylos uva-ursi (L.) Spreng (Bearberry leaf) on the antiallergic and antiinflammatory activities of dexamethasone ointment were investigated. One or 2% UW-ext ointment did not inhibit the ear swelling by picryl chloride-induced contact dermatitis (PC-CD) and carrageenin-induced paw edema. UW-ext augmented the inhibitory effect of dexamethasone ointment (0.005 or 0.025%) on these allergic and inflammatory models, but not the side effect of it. These results suggest that Bearberry leaf increases the inhibitory effect of dexamethasone on the allergic and inflammatory models.     

Non-steroidal antiinflammatory agents. VII. Synthesis and antiinflammatory activity of 5-methyl-10,11-dihydro-5H-pyrrolo [1,2-b] [1,2,5]benzotriazepine-11-acetic acid and its 10-aroyl derivatives

The synthesis of 5-methyl-10,11-dihydro-5H-pyrrolo [1,2-b] [1,2,5]benzotriazepine-11-acetic acid and its 10-aroyl derivatives is reported. Compounds were evaluated for antiinflammatory activity by the carrageenin-induced rat paw edema method. Antinociceptic activity was tested by the hot plate and Randall-Selitto tests. General neuropsychopharmacological effects were also screened. All test compounds showed antiinflammatory effect comparable to that of tolmetin.     

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.

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.     

Basic pharmacological properties of a novel antiinflammatory drug tryptamide

In rats and mice the basic pharmacological properties of tryptamide (TRP), a novel antiinflammatory substance were studied. The LD50 doses were for male rats 1260 mg/kg ip or 8.5 g/kg po, for male mice: 1980 mg/kg ip or 9.3 g/kg po. TRP produced evident antiinflammatory effects of potency comparable with those of phenylbutazone when studied by means of carrageenin-induced rat paw oedema and prostaglandin synthetase activity in vitro. TRP reversed pyrogen-induced hyperthermia in rats, elicited analgesic effects in rats, but not in mice, prolonged the time of hexobarbital sleep in rats and inhibited locomotor activity in rats and mice. TRP has not elicited side effects on the circulatory system of rats and cats. It is concluded that TRP may undergo clinical trials as a potential antiinflammatory drug. During these trials the attention should be paid to possible central side effects the drug.     

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido [1,2-a] pyrimidine-3-carboxamide (Chinoin-127), a potent non-narcotic analgesic and antiinflammatory agent.

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.     

大叶秦艽花与麻花秦艽花抗炎镇痛作用的研究

目的研究大叶秦艽花与麻花秦艽花的抗炎镇痛作用。方法采用二甲苯所致小鼠耳肿胀和大鼠角叉菜胶足趾肿胀模型,研究大叶秦艽花与麻花秦艽花的抗炎作用;采用热板法、醋酸扭体法、光照甩尾法,研究大叶秦艽与麻花秦艽的镇痛作用。结果大叶秦艽、麻花秦艽能减轻二甲苯所致小鼠耳肿胀的体积和大鼠角叉菜胶足趾肿胀率;提高热板法引起小鼠的痛阈值及延长光电甩尾法所致的潜伏期;显著地减少醋酸引起的扭体次数。结论大叶秦艽花与麻花秦艽花具有较好的抗炎、镇痛作用。     

Effects of antiinflammatory agents on rat paw tuberculin response

A marked tuberculin response as well as carrageenin edema were induced in rat hind paw to compare the effects of antiinflammatory agents on these responses. Non-steroidal antiinflammatory agents such as diclofenac and piroxicam were very weak inhibitors of the paw tuberculin response. These agents showed only a slight inhibitory effect on tuberculin response even at doses that were four to five times larger than the 50% effective doses for inhibiting carrageenin edema. On the other hand, steroidal antiinflammatory agents, dexamethasone and prednisolone, showed potent inhibitory effects on the paw tuberculin response at the 50% effective doses for inhibiting carrageenin edema. The above findings clearly revealed the difference in characters between non-steroids and steroids by comparing their effects on tuberculin response and carrageenin edema. The different properties of two classes of antiinflammatory drugs may be of significance in evaluating the effect of antiinflammatory agents on delayed-type hypersensitivity.     

Pharmacological study on piperine

Systematic pharmacological studies on piperine have revealed that this compound elicited diverse pharmacological activities; CNS depressant activity characterized by antagonism against electroshock seizure and by muscle relaxant activity in mice; antipyretic activity in typhoid vaccinated rabbits; analgesic activity as evaluated by tail-clip pressure and writhing syndrome in mice; antiinflammatory activity in carrageenin-induced edema in rats.     

Anti-inflammatory and immunomodulating effects of the novel agent gamma-(2-aminoethylamino)-2-butyrothienone. 1st communication: inhibitory effects on mouse paw edema

A series of 4-hydroxy-(or-amino)-ethyl-amino butyrophenones or butyrothienones were synthesized. For detail studies on antiinflammatory effects, gamma-(2-aminoethylamino)-2-butyrothienone (gamma-ABT) was chosen as representative of these new non-steroidal anti-inflammatories (NSAID). The effect on mouse paw edema induced by various phlogistic agents was first investigated. The inhibitory effect of gamma-ABT on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. Similarly to indometacin, gamma-ABT inhibited the early and late stage of yeast-induced edema in contrast to concanavalin A (Con A) induced edema which was only inhibited by gamma-ABT. Both the above induced edema are supposed to be unrelated to prostaglandins in the rat system. gamma-ABT displayed an inhibitory effect on nystatin-induced edema similar to indometacin suggesting that gamma-ABT has significant membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. gamma-ABT inhibited as well the sustained edema induced by mustard. In conclusion gamma-ABT is an effective agent not only on acute but also on subacute and chronic inflammation and its mode of action appears similar to other NSAID. gamma-ABT posses in addition the advantage of antioxidant activity which is not shared by selective cyclooxygenase inhibitors and thus should be potentially effective in autoimmune diseases.     

Antiinflammatory and antiallergic effects of a novel metabolite of Nocardiopsis sp. as a potent protein kinase C inhibitor from microbial origin

The antiallergic and antiinflammatory effects of the new protein kinase C and calmodulin inhibitor K-252a (8R, 9S, 11S)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11- epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]cycl oocta [cde] trinden-1-one) were investigated in animal models, and the following results were obtained: 1. Oral administration of K-252a, ketotifen or oxatomide showed a dose-dependent inhibition on 48 h homologous passive cutaneous anaphylaxis in rats and anaphylactic bronchoconstriction in passively sensitized guinea pigs. 2. K-252a (1-100 mg/kg p.o.) exerted a dose-dependent protection against platelet-activating factor (PAF)-induced mortality in mice. This protective effect of K-252a was sustained for 7 h. 3. K-252a (1-100 mg/kg p.o.), as well as dexamethasone (1 mg/kg s.c.), showed remarkable inhibitory effects on rat paw edema induced by carrageenin, zymosan, PAF, and antigen-antibody reaction (passive Arthus reaction) and on the croton oil-induced rat ear edema. On the other hand, indomethacin (10 mg/kg p.o.) significantly inhibited carrageenin-induced edema, but did not inhibit edema induced by other phlogistic agents. Based on these results it is suggested that K-252a, by oral administration, has antiallergic and antiinflammatory effects.     

Pharmacological studies on ginger. IV. Effect of (6)-shogaol on the arachidonic cascade

(6)-Shogaol, a pungent component of ginger, which is contained in semi-dried ginger but is rarely found in fresh ginger inhibited carrageenin-induced swelling of hind paw in rats and arachidonic acid (AA)-induced platelet aggregation in rabbits. Moreover, (6)-shogaol prevented prostaglandin I2 (PGI2) release from the aorta of rats when tested as an inhibitor of platelet aggregation. These results suggest that (6)-shogaol may have an inhibitory action on the cyclo-oxygenases in both platelets and aorta. Examination of the effects of (6)-shogaol on cyclo-oxygenases in rabbit platelets and microsome fractions of rat aorta indicated that (6)-shogaol inhibited cyclo-oxygenase activities of both tissues in a concentration-dependent manner. Furthermore, when we examined the effect of (6)-shogaol on 5-lipoxygenase from RBL-1 cells, (6)-shogaol exhibited an inhibitory action on 5-lipoxygenase activity. Therefore, it seems that the inhibitory effects of (6)-shogaol on the carrageenin-induced paw edema, AA-induced platelet aggregation and PGI2 production of aorta may be caused by the inhibition of cyclo-oxygenase activity.     

阿魏洛芬的抗炎镇痛抗肿瘤作用

肌注或腹腔注射阿魏洛芬对小鼠二甲苯耳廓炎症、大鼠角叉菜胶性足肿胀和急性胸膜炎以及巴豆油性肉芽肿均有明显抗炎作用(剂量范围在50～100mg/kg之间,并呈一定的量效关系。对小鼠醋酸扭体反应和光辐射性疼痛型亦显示较强的镇痛效应(100～300mg/kg)。其体外(艾氏腹水癌)体内(S180实体瘤)抑瘤结果表明对前者抑制率高于后者。提示该药可能成为较有希望的非甾体类抗炎抗肿瘤药物。