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Biomedical subjects

M E Rosenthale

Publications and source records attributed to M E Rosenthale.

At least 37 records · Page 2Linked to original sources
PubMed1983

Introduction to the pharmacology of suprofen.

A number of peripherally acting analgesics have become available in the past two decades for the treatment of mild to moderate pain of diverse etiology. The action of these agents is based on their putative ability to inhibit prostaglandin biosynthesis and attenuate hyperalgesia. Suprofen is a new and potent peripherally acting analgesic with anti-inflammatory and antipyretic properties which appears to inhibit prostaglandin synthetase in a tissue-selective manner. In preclinical studies, suprofen was shown to possess a wide separation of analgesic activity from gastrointestinal irritation. Suprofen appears to exert its pharmacological effect by inhibiting synthesis of prostaglandins from precursor arachidonic acid, inhibiting the pain induced by bradykinin, and by raising the threshold to pain induced by prostaglandins. The onset of action is rapid with peak analgesic effect reached in 1-2 h. Preclinical data suggest that suprofen may be an extremely valuable and versatile analgesic for the clinical management of pain.

Animals↗
PubMed1982

Bronchodilator and antiallergic effects of thiazinamium chloride in guinea pigs, rats, cats and dogs.

This study characterized the in vivo pulmonary pharmacology of thiazinamium chloride administered largely by the aerosol route in different animal species. The compound has greater anticholinergic but weaker antihistaminic activity than promethazine, the parent compound. It was less potent than atropine or ipratropium as an anticholinergic and had a shorter duration of action, but unlike these compounds it had long-lasting antihistaminic activity. It is effective in both IgG- and IgE-induced models of passive lung anaphylaxis in guinea pigs and rats, respectively. In Ascaris-induced allergic asthma in the conscious dog it produced a dose-related inhibition of the antigen-induced bronchospasm. No major side effects were observed in acute oral and inhalation toxicity studies in guinea pigs or rhesus monkeys. The results demonstrate that thiazinamium chloride is a safe, potent and efficacious bronchodilator after aerosol administration, with a rapid onset and moderate duration of action in animal models.

Anaphylaxis↗
PubMed1982

Ascaris-induced allergic asthma in the conscious dog: a model for the pharmacologic modulation of immediate type hypersensitivity.

A noninvasive method has been described for producing and assessing Ascaris-induced bronchospasm in the conscious dog and the bronchial responsiveness of a colony of Ascaris-sensitive dogs has been examined over a 2 year period. Both individual and dog-to-dog variation are apparent from the study but the results differ from those of equivalent studies performed by others using anesthetized dogs in that sudden death is not observed. Furthermore, the responses to antigen are not influenced by anesthesia, a procedure that suppresses airway reactivity and pulmonary reflexes. The histamine sensitivity also varied considerably with the different dogs and this corresponded to the sensitivity of the dogs to Ascaris antigen. This model of immediate type hypersensitivity has been used to investigate the effects of bronchodilator and antiallergic drugs.

Animals↗
PubMed1982

Adjuvant arthritis: immunopathological and hyperalgesic features.

Adjuvant arthritis is an experimental immunopathy that is thought to share many features of human rheumatoid arthritis and, as such, is one of the most widely used models for studying the anti-inflammatory properties of compounds. Adjuvant arthritis can be induced in the rat by the injection of various bacterial cell walls or their components; however, the exact immunogen remains unknown. Recently, an autoantibody response to type II collagen was described not only in the collagen-induced arthritic model but in the adjuvant-induced disease as well. This response thus suggests that shared antigenic determinants exist between type II collagen and the responsible immunogen in the bacterial cell wall components. The contribution of the T lymphocyte to the pathogenesis of adjuvant arthritis is well known. It has now been shown that under specific conditions, adjuvant arthritis can be either enhanced or suppressed with pharmacologic or surgical manipulation, thus suggesting the heterogenicity of T lymphocytes capable of influencing the course of the disease. Levamisole was shown to reverse the augmentation of adjuvant disease seen after adult thymectomy, which suggests that levamisole can restore an aberrant immune response. Monoclonal antibodies are now being developed to evaluate T cell subsets in the rat. The use of these antibodies to study or selectively deplete lymphocyte subpopulations in this disease model promises to reveal immunologic characteristics that may lead to the development of new classes of immunoregulant drugs. Finally, the adjuvant rat has been found useful as a pain model capable of detecting the analgesic properties of both central and the newer peripheral analgesics. The above studies further corroborate the similarities between the immunopathological and hyperalgesic features of human rheumatoid arthritis and adjuvant disease. Recently developed immunologic technology may allow a new look at an old model and may result in the ability to evaluate new classes of immunoregulating agents.

Animals↗
PubMed1982

The pharmacologic profile of wy-41,195, a new orally effective antiallergic agent.

[2-Cyano-3-(methylamino)phenylamino]oxoacetic acid, sodium salt (Wy-41,195) was found to be a potent oral inhibitor (viz., ED50, 0.3 mg/kg) of IgE-mediated release in the rat passive cutaneous anaphylaxis (PCA) model and was very effective by the aerosol and oral route in the rat passive lung anaphylaxis model. High doses (25-50 mg/kg p.o.) were effective when administered up to 180 min before antigen challenge in the rat PCA model. The compound had minimal phosphodiesterase activity and demonstrated no bronchodilator or antihistamine activity. In the dog, Wy-41,195 inhibited histamine-induced reflex bronchoconstriction but had little effect on Ascaris-induced bronchoconstriction. No significant ancillary pharmacology was observed for Wy-41,195 except for inhibition of gastric secretion in the rat. The compound is relatively nontoxic and possesses a very high therapeutic index (greater than 10 000). Activity in these animal systems indicates that Wy-41,195 may hold promise in the treatment of bronchial asthma and other allergic diseases in man.

Amino Acids↗
PubMed1981

SRS-A mediated bronchospasm by pharmacologic modification of lung anaphylaxis in vivo.

Antigen challenge of actively sensitized guinea pigs results in the release of histamine eicosanoids (products of the cyclooxygenase pathway of arachidonic acid metabolism) and slow reducing substance of anaphylaxis (SRS-A). By antagonizing the effects of histamine, serotonin, and acetylcholine, inhibiting the cyclooxygenase pathway and supplying arachidonic acid as substrate, the contribution of SRS-A to anaphylactic bronchospasm can be enhanced, thus allowing suitable quantitation of antagonists. This SRS-A mediated bronchospasm can be inhibited in a dose dependent fashion by FPL55712, a selective antagonist of SRS-A. This system represents an in vivo method capable of detecting compounds which inhibit SRS-A synthesis/release of SRS-A action at the effector organ.

Anaphylaxis↗
PubMed1980

Immunopharmacologic properties of 1,6-bis[2-(diethylamino)ethoxy]xanthen-9-one dihydrochloride (Wy-15297).

When tested in a series of immunopharmacologic assays, the interferon inducer, WY-15297, was shown to lack activity in early vascular and humoral phases of the inflammatory response, while it was quite effective against the immunologic phase. The profile of activity of Wy-15927 was, however, unlike those previously described for reference antiinflammatory and immunosuppressive drugs and this may represent one of a new class of immunopharmacologic agents capable of selectively modulating the lymphoreticular system.

Animals↗
PubMed1980

Suprofen, a new peripheral analgesic.

The antinociceptive properties of suprofen [alpha-methyl-4-(thienylcarbonyl)benzene acetic acid] are described in a pathologically induced hyperalgesic model, the rat adjuvant arthritis flexion test. By using this assay, suprofen was characterized as an orally effective, non-narcotic analgesic with a rapid onset and 4-hr duration of activity. Suprofen is 50 times more potent than acetaminophen, five times more potent than codeine and equipotent to the new peripheral analgesics, zomepirac and diflunisal. In combination experiments, suprofen potentiates the analgesic effects of acetaminophen and, unlike morphine, the analgesic effect of suprofen is not blocked by naloxone. In other hyperalgesic assays, suprofen is an extremely potent inhibitor of arachidonate-induced writhing and is equipotent to morphine in the yeast-induced paw edema (Randall-Selitto) assay. Additionally, suprofen is inactive on the normal paw in the Randall-Selitto test, the mouse Eddy hot-plate test and the tail withdrawal reflex assay induced by warm water in rats, all sensitive tests capable of detecting central (narcotic) but not peripheral analgesics. Activity on prostaglandin biosynthesis from several species and tissues suggests that suprofen is a tissue selective inhibitor of prostaglandin synthesis. These experiments suggest that suprofen represents a new class of potent, orally effective, peripheral (non-narcotic) analgesics with potential usefulness in a variety of clinical pain situations formerly reserved for narcotics.

Acetaminophen↗
PubMed1976

Immunopharmacologic properties of WY-16,922, a new orally effective antiallergic agent.

In a series of tests designed to illustrate immune reactions similar to those obtained in atopic disease, Wy-16,922 effectively inhibited reaginic-mediated immunologic reactions in the skin, longs and mast cell. It was found to be devoid of immunosuppressant, antimediator, anti-inflammatory, steroid or bronchodilator properties as well as acute toxicity. Although the mechanism of action Wy-16,922 is unknown, it appears to limit the release (not the effects) of allergic mediators in a manner similar to that described for disodium cromoglycate.

Anaphylaxis↗
PubMed1976

Immunopharmacologic properties of WY-16, 922, a new orally effective antiallergic agent.

In a series of tests designed to illustrate immune reactions similar to those obtained in atopic disease, Wy-16,922 effectively inhibited reaginic-mediated immunologic reactions in the skin, lungs and mast cell. It was found to be devoid of immunosuppressant, antimediator, anti-inflammatory, steroid or bronchodilator properties as well as acute toxicity. Although the mechanism of action of Wy-16,922 is unknown, it appears to limit the release (not the effects) of allergic mediators in a manner similar to that described for disodium cromoglycate.

Anaphylaxis↗
PubMed1976

Actions of prostaglandins on the respiratory tract of animals.

Experimental data now strongly suggest that the PGs, by nature of their natural local occurrence and destruction, powerful effects on, and release from lung tissue are important in regulating both pulmonary homeostasis and dysfunction. Laboratory studies on their activity, potency, duration, preferred route of administration, mechanism and possible antiallergic effects, have been largely substantiated in humans. Structure activity studies on a large number of congeners of PGE, PGF, and PGA emphasize the critical importance of stereochemistry and various substituent groups on biologic activity in the lung.

Aerosols↗
PubMed1975

Animal pharmacology of Wy-16,225, a new analgesic agent.

The analgesic potency of Wy-16,225 in rodents and primates is greater than morphine while antagonist potency is slightly less than that of nalorphine. The compound demonstrates properties unlike those of standard narcotic and narcotic antagonist agents and has a wide margin of safety. In dependence liability studies, Wy-16,225 neither acutely substitutes for morphine nor produces direct dependence when administered chronically to monkeys. Wy-16,225 has no anti-inflammatory properties, is not constipating in rats, has no significant cardiovascular toxicity in dogs and produces minimal respiratory depression in monkeys.

Analgesics↗