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[Contribution on a method of evaluating the analgesic action of drugs].
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A secondary amine producing analgesia in humans.
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Preliminary clinical report o a new analgesic.
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[The synthetic analgesics].
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Causes of chromosome anomalies suggested by cytogenetic epidemiology of induced abortions.
Women who visited hospitals requesting induced abortions were asked about their obstetric and medical histories by attending physicians prior to the operation. The information was solely based on their reports at the interview. The period of coverage was nine weeks, comprising six weeks before and three weeks after the onset of the last menstruation. Both the occurrence of acute respiratory infectious diseases, which included the common cold, upper respiratory tract infection (U.R.T.I.), influenza, and pneumonia, and the use of analgesics and antipyretics were most frequently reported. Regardless of whether they had an acute respiratory illness, the women who took analgesics and antipyretics (including antihistamine, cough remedy, and nasal decongestant) had 13.8% (8/58) gross chromosome anomalies. The women without the treatment had 6.3% (71/1136) anomalies. The difference was statistically significant (P less than 0.05). Triploid formation was particularly related to drug consumption, thus there were 5.2% (3/58) in the treated group and 0.5% (6/1136) in the untreated group (P=0.0074). In contrast, trisomy was not considered to be related to drug consumption on account of 8.6% (5/58) and 4.1% (47/1136) in the corresponding groups (0.10 less than P less than 0.20). When the occurrence of trisomy was examined in connection with two variables, i.e., the presence of drug consumption and the age of mothers, association was not evident (X2 assoc. = 0.883, d.f. = 1 by Cochran's method). Besides these results, neither maternal X-irradiation nor irregularity of the menstrual period was found to be related to the frequency of chromosome anomalies in the progeny.
The analgesic activity of imidazopyridine derivatives.
Analgesic and antipyretic activities of 2-(4-(2-imidazo-[1,2-a]pyridylphenyl)propionic acid (Y-9213) were studied with various experimental models. The analgesic activity of Y-9213 was found to be more potent than that of indometacin and morphine in the silver nitrate, Randall-Selitto, and phenylquinone writhing tests. Y-9213 also showed an analgesia in the tail pinch and electric stimulation test. On the warm water induced foot withdrawal reflex, Y-9213 was more effective in spinal-sectioned mice than in intact mice similarly to mephenesin and diazepam. Y-9213 was also proved to possess antipyretic activity as potent as indometacin and to be devoid of morphine-like property. Y-9213 exhibited little effect on the respiration and cardiovascular system in dogs. Y-9213 was found to be rapidly absorbed and eliminated from the blood with a half-life of about 2.5 h in rats. These findings indicate that Y-9213 may be an effective and well tolerated antipyretic and analgesic agent.
Spinal actions of nonsteroidal anti-inflammatory drugs.
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the signs and symptoms of inflammation. They originated from man's early use of willow bark in the treatment of rheumatism. Although these drugs have been developed because of their effects on arthritis, their substantial analgesic and antipyretic actions have led to their widespread application. The NSAIDs are classified on the basis of their chemical structure under the category of acidic and nonacidic agents. The anti-inflammatory, analgesic and antipyretic effects of NSAIDs are attributable to their suppression of prostaglandin synthesis activity through cyclooxygenase inhibition. Regarding the analgesic effects of NSAIDs, initially, the peripheral mechanism was proposed. It has been assumed that the effects result from inhibition of the synthesis of prostaglandins in the peripheral inflamed tissue because prostaglandin may sensitize the peripheral nociceptors to the effects of other mediators released from the inflamed tissue. However, the central mechanism, acting within supraspinal or spinal level, was also suggested recently. Their exact sites and modes of action within the spinal cord are poorly defined, and even controversial. There are two main hypotheses to elucidate this issue. One is that the spinal analgesic actions are associated with prostaglandins synthesis, because of the excitatory effect of prostaglandins in the spinal cord and the other is dissociated from prostaglandins synthesis, and their effect may be related to their ability to affect the spinal nociceptive, processing cellularly or intracellularly. However, both mechanisms are probably linked. In conclusion, although the real mechanisms of the spinal analgesic actions of NSAIDs remain unclear, further basic and clinical studies should be made. In this way, we may hopefully provide more opportunities for effective pain management.
The absolute antipodal activity of analgesics in the basic anilide series.
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Childhood cancers and their association with pregnancy drugs and illnesses.
In a case/control study of 8059 matched pairs, the effect of maternal exposure to drugs and illnesses during pregnancy on the relative risk (RR) of cancer in the child was investigated using conditional logistic regression techniques. Acute respiratory infections, particularly viral infections such as influenza, were associated with a significantly increased RR of all childhood cancers and of neoplasms of the reticulo-endothelial system (RES) in particular, (RR = 1.69 all cancers, RR = 1.81 RES neoplasms, RR = 1.59 solid cancers). An analysis of illnesses according to their physiological effects yielded a significant association between childhood leukaemia and febrile illnesses (RR = 1.27 RES neoplasms). A significant increase in RR was associated with maternal history of epilepsy (RR = 1.31 all cancers) rather than with exposure to anticonvulsant drugs. Vaccines showed a pattern of RR similar to that of acute viral infections. Consumption of antipyretics and analgesics significantly increased the RR of childhood cancer (RR = 1.36 all cancers). An analysis of drugs according to their metabolic reactions yielded a significant association between those undergoing amino acid conjugation (predominantly antipyretics and analgesics) and childhood cancer risk (RR = 1.76 solid cancers).
Evaluation of Artemisia inculta for anti-inflammatory activity in rats.
The ethanolic extract of Artemisia inculta has been screened for anti-inflammatory, analgesic and antipyretic activities on suitable experimental models. It has been found to produce significant inhibition of carrageenan induced paw edema and cotton pellet induced granuloma pouch and a significant decrease in the prothrombin time in rats. It failed to produce any analgesic or antipyretic activity on the hot plate reaction time and yeast induced hypyrexia tests in mice. It also did not produce any effect on the platelet aggregation and fibrinogen level in the rats. Amongst the phytoconstituents detected in this plant, flavonoids may be responsible for the observed anti-inflammatory effect of the ethanolic extract.
[Studies on the analgesics. I. The pharmacological effects of acyl derivatives of aminoalkylaniline].
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Evaluation of a new anti-inflammatory/analgesic compound F-776, 5-(4-chlorophenyl)-beta-hydroxy-2-furanpropanoic acid.
F-776, 5-(4-chlorophenyl)-beta-hydroxy-2-furanpropanoic acid, is a nonsteroidal anti-inflammatory, analgesic, and antipyretic drug which does not produce stomach ulcers. It's spectrum of activity includes full anti-inflammatory efficacy in bilaterally adrenalectomized rats; and ED50 value in the carrageenin hindpaw edema assay comparable to that of fenoprofen and ibuprofen; effectiveness in preventing and in diminishing developing and established adjuvant-induced polyarthritis in rats, respectively; significant reduction of granulation tissue formation around cotton pellets; significant decrease in erythema resulting from ultraviolet irradiation of guinea-pig skin; analgesia as determined in the rat paw pressure procedure; antipyretic activity in rats with yeast-induced fever; and an uricosuric effect noted at higher than anti-inflammatory doses. F-776 is not an immunosuppressant as determined in the experimental allergic encephalomyelitis rat model. Its mechanism of action is as yet undetermined. In conclusion, F-776 represents a new nonulcerogenic anti-inflammatory, analgesic, and antipyretic compound with potential utility in different arthritic conditions.
Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: combination therapy with antisecretory agents in rats.
BACKGROUND & AIMS: The gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are reduced by antisecretory agents. The effects of combination therapy on the gastrointestinal toxicity and therapeutic activity of free and phospholipid-associated NSAIDs were investigated in rats. METHODS: Fasted rats, pretreated with either saline or an antisecretory dose of omeprazole, ranitidine, or cimetidine, were intragastrically administered saline, aspirin, or indomethacin. In ulcer models, gastric lesions in aspirin-treated rats and intestinal bleeding in indomethacin-treated rats were measured. For antipyretic and analgesic activity, rectal body temperature in febrile rats and the rats' pain sensitivity to pressure applied to an inflamed limb were measured, respectively. RESULTS: NSAID-induced gastrointestinal ulceration and bleeding were reduced in rats pretreated with antisecretory agents and abolished in rats administered phospholipid-associated NSAIDs in combination with inhibitors of acid secretion. The antipyretic and analgesic activity of both NSAIDs was attenuated in rats pretreated with an antisecretory agent. This pH-dependent block in therapeutic activity was overcome if the NSAID was preassociated with a phospholipid to enhance the drug's lipophilic characteristics. CONCLUSIONS: Combination therapy of antisecretory agents and NSAIDs, chemically associated with phospholipids, has distinct advantages with regard to both low gastrointestinal toxicity and restored therapeutic activity.
Anti-inflammatory activity of some Saudi Arabian medicinal plants.
Five plants which have been used for the treatment of rheumatism, arthritis and gout in the traditional medicine of Saudi Arabia, were evaluated for their anti-inflammatory properties. Of these the ethanolic extract of Capparis decidua and the aqueous extract of Capparis spinosa were found to possess significant anti-inflammatory activity against carrageenan induced oedema in rats. These two plants were also tested for their antipyretic and analgesic activity. C. decidua was found to possess significant antipyretic effect. Both of them are devoid of analgesic activity.
Pharmacological and toxicological studies with 1-benzyl-3-(2,3-dihydroxypropoxy)indazole.
1-Benzyl-3-(2,3-dihydroxypropoxy)-indazole (benzidol) is a novel indazolane derivative with marked antiinflammatory, analgesic and antipyretic properties. Its acute toxicity is three times less than that of benzidamine and five times less than that of phenylbutazone. Rats, mice, guinea pigs and rabbits treated with benzidol during 6 months at doses of 5, 50 and 200 mg/kg did not present any pathological alteration. The anti-inflammatory activity of benzidol is similar to that of phenylbutazone and higher than that of benzidamine. The analgesic and antipyretic properties are also considerable. Benzidol is better tolerated than the mentioned drugs with similar activities.