Pharmacological studies of dl-2[3-(2'-chlorophenoxy)phenyl]propionic acid. I. Analgesic and antipyretic effects

Analgesic and antipyretic effects of dl-2[3-(2'-chlorophenoxy)phenyl] propionic acid (CPP) were studied in mice, rats and guinea-pigs. CPP produced a dose dependent inhibition of acetic acid-induced writhing syndrome. Its ED50 values 1 and 3 hr after oral administration were 47 and 31 mg/kg, respectively. CPP had a potent analgesic effect on bradykinin-induced nociceptive response in rats, and its ED50 value was 15 mg/kg 2 hr after oral administration. The analgesic activity of CPP in these experiments was less potent than that of indomethacin, but it was approximately equivalent to ibuprofen and 10 to 20 times as potent as aspirin. CPP had no analgesic effect on both the tail pinch and hot plate tests in mice, while CPP potentiated the analgesic effect of codeine on these tests. CPP had no effect on the nociceptive response induced by intradermal injection of bradykinin and/or EDTA in guinea-pigs. On the other hand, when CPP was given orally in a dose range of 1.25 to 5 mg/kg, it produced an antipyretic effect on yeast-induced fever in rats. The antipyretic activity of CPP was equivalent to ibuprofen and 10 to 15 times as potent as aspirin.     

去氧乌头碱的抗炎、镇痛和解热作用

本文报告了新近以伏毛铁棒锤中提得的去氧乌头碱(DAC)的抗炎、镇痛和解热作用实验结果,并与已报道过的3-乙酰乌头碱(3AAC)进行比较。DAC0.8mg/kg (ip)显著抑制巴豆油所致小鼠耳廓肿;0.2mg/kg(ip或sc)显著抑制角叉菜胶或甲醛所致大鼠足爪肿、组胺所致大鼠皮肤渗出及醋酸所致小鼠腹腔渗出。于大鼠角叉菜胶足爪肿模型,测得DAC(ip)的抗炎治疗指数(6.38)略高于3AAC(5.92)。醋酸扭体法测得DAC抑制小鼠扭体反应50％的剂量为0.22±0.06mg/kg(sc);热板法测得DAC的小鼠镇痛ED_(50)为0.41±0.10mg/kg(ip),其镇痛治疗指数(6.37)高于3AAC(4.60)。DAC0.24mg/kg(ip)对伤寒副伤寒混合菌苗所致家兔发热有显著解热作用。     

Pharmacological studies on 3-[gamma-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1-(H)-pyrazino(1,2-a)quinoline hydrochloride (compound 69/183). Part IV: other CNS effects and acute toxicity

3-[gamma-(p-Fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1-(H)-pyrazino(1,2-a)quinoline hydrochloride (centpyraquin), a potent antihypertensive and tranquillising agent, was tested for anticonvulsant, analgesic and anti-inflammatory activities in mice and for anti-emetic activity in dogs. It did not modify supramaximal electroshock seizures and failed to protect the animals against pentylenetetrazole and strychnine induced convulsions. It, however, produced some elevation in the threshold dose of strychnine. Tremorine induced tremors and salivation were not antagonised. The compound had weak analgesic activity as detected by antagonism to phenylquinone writhing and the hot plate test. It had no anti-inflammatory activity. Centpyraquin had strong anti-emetic activity against apomorphine as well as morphine. At high doses it produced fall out in the rota-rod test. The LD50 of centpyraquin in mice was 296 mg/kg i.p. and more than 1000 mg/kg p.o. and in rats it was 161 mg/kg i.p. and more than 800 mg/kg p.o. The observed CNS effects resemble those of other neuroleptics.     

Analgesic and anti-inflammatory activities in rats of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its intestinal damage

alpha-(3,5-Di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), an anti-inflammatory drug, possesses analgesic activity in rat models. In the acetic acid-induced writhing test, the oral ED50 values for KME-4, indomethacin, naproxen and ibuprofen were 5.2, 3.8, 7.0 and 18.6 mg kg-1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid-induced vascular permeability in rats. KME-4 also had analgesic activity in the tests of Randall-Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME-4 (10 mg kg-1 day-1 orally) has a preventive effect against adjuvant-induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg-1 day-1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME-4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen.     

Antidiarrheal and anti-inflammatory effects of berberine

Berberine sulfate (Ber) 40 and 80 mg/kg ig reduced the purging effects of castor oil or Cassia angustifolia leaf in mice, but did not affect the gastrointestinal transport function of Chinese ink in normal mice. Ber 60 mg/kg ig significantly inhibited the increased vascular permeability induced by ip 0.7% acetic acid in mice. Ber 20 and 50 mg/kg sc markedly inhibited the increased vascular permeability induced by histamine 100 micrograms/0.1 ml ic in rats. Ber 4 and 8 mg/kg sc produced obvious inhibition in the xylene-induced swelling of mouse ear. The anti-inflammatory effects were enhanced in a dose-dependent manner. It is suggested that the antidiarrheal effect of Ber is relative to its restriction against exudative inflammation to a certain extent.     

Evaluation of the anti-inflammatory property of the extract of <Emphasis Type="Italic">Combretum micranthum</Emphasis> G. Don (Combretaceae)

A methanol extract of Combretum micranthum leaves was studied for anti-inflammatory activity in rats and mice using the carrageenan-induced rat paw oedema and the acetic acid-induced vascular permeability in mice. The effect of the extract on cellular-type inflammation was also investigated in the cotton pellet granuloma in rats. The extract (50, 100 mg/kg) significantly (P < 0.05) inhibited oedema production induced by carrageenan in rats. Increased vascular permeability caused by acetic acid injection was also inhibited by the extract, within the same dose range. C. micranthum extract (100 mg/kg) inhibited granuloma formation in rats to a similar degree as indomethacin (5 mg/kg). These results provide evidence for the anti-inflammatory property of C. micranthum leaves.     

Analgesic, anti-inflammatory and hypoglycaemic effects of Securidaca longepedunculata (Fresen.) [Polygalaceae] root-bark aqueous extract

The present study was undertaken to investigate the analgesic, anti-inflammatory and hypoglycaemic properties of Securidaca longepedunculata (Fresen.) root-bark aqueous extract (SLE) in mice and rats. The analgesic effect of SLE was evaluated by 'hot-plate' and 'acetic acid' analgesic test methods in mice; while its anti-inflammatory and hypoglycaemic effects were examined in rats, using fresh egg albumin-induced pedal oedema, and streptozotocin (STZ)-induced diabetes mellitus models. Morphine (MPN, 10 mg/kg), diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used as reference drugs for comparison. SLE (50-800 mg/kg i. p.) produced dose-dependent, significant (p < 0.05-0.001) analgesic effects against thermally- and chemically-induced nociceptive pain in mice. The plant's extract (SLE, 50-800 mg/kg p. o.) also dose-dependently and significantly inhibited (p < 0.05-0.001) fresh egg albumin-induced acute inflammation, and caused significant hypoglycaemia (p < 0.05-0.001) in normal (normoglycaemic) and STZ-treated diabetic (hyperglycaemic) rats. The results of this experimental animal study indicate that S. longepedunculata root-bark aqueous extract (SLE) possesses analgesic, anti-inflammatory and hypoglycaemic properties. These findings lend pharmacological credence to the anecdotal, folkloric and ethnomedical uses of S. longepedunculata root-bark in the treatment, management and/or control of painful, arthritic, inflammatory conditions, as well as in the management and/or control of type 2 diabetes mellitus in some rural communities of South Africa.     

Effects of ipriflavone (TC-80, an anti-osteoporotic drug) on acute and chronic pain

The effects of TC-80 on acute and chronic pain in rats and mice were examined. Single oral administration of TC-80 at 50-300 mg/kg was not analgesic in the phenylquinone writhing, acetic acid writhing, and hot plate tests in mice or the tail flick test in rats. Three-weeks administration of TC-80 in a dose of 100 mg/kg/day, p.o., to rats had no analgesic action in the acetic acid writhing and tail flick tests. When TC-80 was given orally in a dose of 100 mg/kg/day for 3 weeks to rats with adjuvant arthritic chronic pain, analgesic effects were observed 2 weeks after the start of administration in males and in ovariectomized estrone-supplemented females; the effect seen in the females was statistically significant. Changes in the bones of the hind paws were examined radiologically, and synovitis, periosteal new bone formation and bone destruction were examined histopathologically in the females. These variables were improved by treatment with TC-80 for 3 weeks. It is concluded that TC-80 has no analgesic effect, but may inhibit chronic pain by anti-osteoporotic action on bone disease.     

Evaluation of the anti-inflammatory and analgesic properties of the extract of Russelia equisetiformis (Schlecht &; Cham) Scrophulariacae

A methanolic extract of Russelia equisetiformis whole plant was studied for anti-inflammatory and analgesic activities in rats and mice using carrageenan-induced rat paw oedema, aceticacid-induced writhing and tail-flick test. The extract, at 10, 20 and 40 mg/kg, significantly (P <0.05) inhibited carrageenan-induced oedema in rats. Abdominal constriction induced by acetic acid was also inhibited by the extract, within the same dose range. The extract at the same dose also prolonged the latency period in the tail-flick response test, which was reverted by naloxone. The results suggested that the extract possesses potential anti-inflammatory and analgesic properties.     

Synthesis and analgesic and anti-inflammatory activities of 1,2-benzothiazine derivatives

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/anti-inflammatory efficacy and their effects on gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent analgesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 mg/kg.     

Analgesic,anti-inflammatory and anti-platelet activities of the methanolic extract of <Emphasis Type="Italic">Acacia modesta</Emphasis> leaves

The current study was aimed to evaluate Acacia modesta for analgesic, anti-inflammatory, and anti-platelet activities. The analgesic and anti-inflammatory effects were assessed in rodents using acetic acid and formalin-induced nociception, hot plate and carrageenan-induced rat paw oedema tests. The intraperitoneal (i.p.) administration of the methanolic extract (50 and 100 mg/kg) produced significant inhibition (P < 0.01) of the acetic acid-induced writhing in mice and suppressed formalin-induced licking response of animals in both phases of the test. In the hot plate assay the plant extract (100 mg/kg) increased pain threshold of mice. Naloxone (5 mg/kg i.p.) partially reversed the analgesic effect of the extract in formalin and hot plate tests. A. modesta (100 and 200 mg/kg i.p.) exhibited sedative effect in barbiturate-induced hypnosis test similar to that produced by diazepam (10 mg/kg i.p.). The plant extract (50–200 mg/kg i.p.) produced marked anti-inflammatory effect in carrageenan-induced rat paw oedema assay comparable to diclofenac and produced a dose-dependent (0.5–2.5 mg/mL) inhibitory effect against arachidonic acid induced platelet aggregation. These data suggest that A. modesta possesses peripheral analgesic and anti-inflammatory properties, with analgesic effects partially associated with the opioid system.     

新型羟基脲化合物Ⅲ_5的镇痛抗炎作用

目的探讨新型羟基脲类化合物Ⅲ5的镇痛及抗炎作用。方法采用小鼠热板法和扭体法证明化合物Ⅲ5的镇痛作用;采用二甲苯致小鼠耳肿胀,醋酸致毛细血管通透性增加,蛋清致大鼠足趾肿胀模型证明化合物Ⅲ5的抗炎作用。结果化合物Ⅲ5能延长小鼠的热痛阈值,能延长造模后小鼠第一次出现扭体反应的潜伏期并减少15 min内扭体反应出现的次数;能显著抑制耳肿胀,醋酸对毛细血管的通透性以及不同时间点大鼠的足趾肿胀度。结论化合物Ⅲ5具有明显的镇痛抗炎作用。     

赖氨匹林的解热、镇痛和抗炎作用

目的：应用大鼠及小鼠研究赖氨匹林的抗炎、镇痛及解热作用。方法：用大鼠足跖肿胀研究抗炎作用，用小鼠醋酸扭体法及热板法测定镇痛作用，用鲜酵母法测定解热作用。结果：赖氨匹林对大鼠足跖肿胀有明显抑制作用，最大抑制率为８０％（Ｐ＜０．０１）。小鼠醋酸扭体法测得镇痛ＥＤ５０＝７２±２３ｍｇ／ｋｇ，对鲜酵母致大鼠体温升高有明显抑制作用。小鼠半数致胃溃疡剂量ＵＤ５０＝０．１８±０．０６ｍｍｏｌ／ｋｇ，是阿司匹林的２．４倍。结论：赖氨匹林具有和阿司匹林相当的解热、镇痛和抗炎作用，而对胃肠道的毒副作用比阿司匹林小。     

Synthesis and anti-inflammatory activity of 3-(benzylideneamino)coumarins in rodents.

A series of substituted 3-(benzylideneamino) coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedmatous activity, respectively (phenylbutazone antiedematous activity, 58%). The analgesic activity of 4g and 4c, based on inhibition of acetic acid-induced writhing in mice (67 and 62%, respectively, at oral doses of 100 mg/kg) was comparable with that of aspirin (58%). However, these derivatives were devoid of antipyretic activity and showed low activity against adjuvant-induced arthritis.     

Inhibitory effect of a pyrrolizidine alkaloid, crotalaburnine, on rat paw oedema and cotton pellet granuloma

1 The anti-inflammatory activity of crotalaburnine (=anacrotine) was investigated against increased vascular permeability and oedema produced by formalin, carrageenin, hyaluronidase, 5-hydroxytryptamine, dextran, bradykinin and prostaglandin, and against formation of granulation tissues by cotton-pellet in rats. The effect was compared with the activity of hydrocortisone, phenylbutazone, sodium salicylate and cyproheptadine against different types of inflammation.2 Crotalaburnine (40 mg/kg s.c. x 5 alternate days) had no significant inhibitory effect against formalin-induced arthritis, while hydrocortisone (40 mg/kg s.c. x 10 days) was effective from the fifth day onwards.3 Against carrageenin-induced oedema both crotalaburnine (10 mg/kg s.c.) and phenylbutazone (100 mg/kg oral) produced a similar degree of inhibition. Hydrocortisone (10 mg/kg s.c.) produced slightly greater inhibition.4 In normal rats crotalaburnine (10 mg/kg s.c.), phenylbutazone (100 mg/kg oral) and sodium salicylate (500 mg/kg i.p.) inhibited hyaluronidase-induced oedema. However, in adrenalectomized rats, there was a reduction of the inhibitory effect of sodium salicylate but not of phenylbutazone or crotalaburnine.5 Crotalaburnine (40 mg/kg s.c. and 30 mg/kg i.p., respectively) was ineffective against 5-hydroxytryptamine- and dextran-induced oedema but against bradykinin- and prostaglandin-induced oedema (in a dose of 20 mg/kg i.p.) it was quite effective. In a parallel series cyproheptadine (10 mg/kg oral and i.p., respectively) produced significant inhibition of 5-hydroxytryptamine- and dextran-induced oedema, while phenylbutazone (100 mg/kg i.p.) failed to produce any significant inhibition of prostaglandin-induced oedema.6 Against cotton-pellet granuloma crotalaburnine, in half the dose of hydrocortisone, produced similar inhibition while phenylbutazone produced much greater inhibition in five times the dose of crotalaburnine given orally.7 The possible mode of action of crotalaburnine as an anti-oedema agent is discussed.     

General pharmacological action of 4-(o-benzylphenoxy)-N-methylamine hydrochloride (bifemelane hydrochloride, MCI-2016)--influence on the central nervous system

General pharmacological action of 4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane hydrochloride, MCI-2016) was examined with regard to the effects mainly on the central nervous system. MCI-2016, at 30-100 mg/kg, p.o., only showed a weak sleep prolongation effect (mice), anti-convulsant action (mice) and a moderate facilitation of exploratory behavior, but produced no remarkable behavioral changes. Above the doses of 200 to 300 mg/kg, p.o., MCI-2016 produced a decrease in muscle or body tone, mydriasis and a slight decrease of locomotor activity. The drug, however, showed little influence on exploratory behavior, conditioned avoidance response and normal body temperature (rats). Normal body temperature in rabbits was also little affected by MCI-2016. Effects on EEG was characterized by moderate activation of spontaneous EEG and potentiation of arousal response by stimulation of the midbrain reticular formation (1.5-5 mg/kg, i.v.). The drug, however, did not significantly change the sleep-wakefulness cycle and REM-sleep in rats. MCI-2016 also showed little influence on spinal reflex potentials and neuromuscular junction at high doses (10 mg/kg, i.v.). These results may indicate that MCI-2016 has slight influence on overall behavioral and motor changes. Effects of MCI-2016 on acetic acid-induced writhing, carrageenin edema and corneal reflex were also examined. MCI-2016 showed moderate analgesic and anti-inflammatory actions at 50-100 mg/kg, p.o., and also showed local anesthetic action. The duration of local anesthetic action was relatively long but the drug produced no local damage.     

3,4-二氢吡咯[1,2-a]吡嗪-1-酮衍生物的合成及抗炎镇痛作用

目的研究(2H)-2-环己基-3,4-二氢吡咯[1,2-a]吡嗪-1-酮衍生物抗炎镇痛作用的构效关系。方法以2-吡咯甲酸甲酯为原料,经取代、环合,制备(2H)-2-环己基-3,4-二氢吡咯[1,2-a]吡嗪-1-酮(3);通过Friedel-Crafts酰基化反应,制得其6-酰基衍生物4a~4j。用小鼠测试了所合成化合物的抗炎和镇痛活性。结果与结论合成了10个未见文献报道的新化合物4a~4j,其结构经MS1、H-NMR分析确证。抗炎镇痛试验表明,有些化合物具有明显的抗炎和/或镇痛作用,其中化合物4d的活性与对照药布洛芬相当。     

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。     

国产湿痛喜康的抗炎解热和镇痛作用

湿痛喜康对角叉菜胶诱发大鼠踝关节肿胀、二甲苯诱导小鼠耳水肿、大鼠佐剂性关节炎、酵母诱发大鼠发热、冰醋酸诱导小鼠扭体反应和“热板”致痛反应等实验模型,有明显的抗炎、解热和镇痛作用。对角叉菜胶性炎症模型和小鼠扭体反应的ED_(50)分别为5.26mg/kg和5.5mg/kg。