ABSTRACT
A topical preparation of meclofenamic acid (Meclomen) was tested for anti-inflammatory activity in a murine model of carrageenan footpad oedema. The preparation significantly inhibited swelling when applied to the carrageenan-injected paw. Maximum inhibition was observed 4-5 h after carrageenan injection. The topical effects could not be attributed to systemic absorption because the preparation was more inhibitory when applied topically to the carrageenan-injected paw than to a distant site or orally.
Subject(s)
Anti-Inflammatory Agents , Meclofenamic Acid/administration & dosage , ortho-Aminobenzoates/administration & dosage , Administration, Oral , Administration, Topical , Animals , Carrageenan , Edema/chemically induced , Edema/drug therapy , Female , Indomethacin/administration & dosage , Mice , Mice, Inbred C57BLSubject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Osteoarthritis/drug therapy , Piroxicam/analogs & derivatives , Thiazines/therapeutic use , Adult , Aged , Animals , Arthritis, Experimental/drug therapy , Clinical Trials as Topic , Collagen , Drug Interactions , Drug Tolerance , Edema/prevention & control , Half-Life , Humans , Kinetics , Muscular Diseases/drug therapy , Oxygenases/antagonists & inhibitors , Rats , Thiazines/adverse effects , Thiazines/metabolism , Thiazines/pharmacologyABSTRACT
N-(2,6-Dichloro-m-tolyl)anthranilic acid, sodium salt (meclofenamate sodium, Meclomen), the sodium salt of meclofenamic acid, has anti-inflammatory activity both in animal models and in clinical use. This activity is believed to be due in large part to the ability of the drug to inhibit the synthesis of prostaglandins by inhibiting arachidonic acid cyclo-oxygenase. Further, there is evidence that meclofenamic acid directly antagonizes the actions of prostaglandins at receptor sites. In addition, meclofenamic acid may also inhibit arachidonic acid lipoxygenase, resulting in decreased synthesis of leukotrienes, known mediators involved in the inflammatory process.
Subject(s)
Meclofenamic Acid/pharmacology , ortho-Aminobenzoates/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal , Edema/drug therapy , Fever/prevention & control , Humans , Prostaglandins/biosynthesis , Receptors, Prostaglandin/metabolism , Vasodilation/drug effectsABSTRACT
Lorazepam reduced conflict behavior in rats and monkeys, inhibited pentylenetetrazol- and electroshock-induced convulsions, suppressed footshock-induced fighting behavior, and prevented morphine-induced stimulation in mice at lower doses than other benzodiazepines tested. This behavioral profile suggests that lorazepam will be an active anti-anxiety agent in man at low doses.
Subject(s)
Anti-Anxiety Agents/pharmacology , Lorazepam/pharmacology , Aggression/drug effects , Animals , Avoidance Learning/drug effects , Behavior, Animal/drug effects , Cats , Conditioning, Operant/drug effects , Differential Threshold , Discrimination Learning/drug effects , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Haplorhini , Humans , Male , Mice , Motor Activity/drug effects , Rats , Reflex/drug effects , Saimiri , Seizures/etiology , Seizures/prevention & controlABSTRACT
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.
Subject(s)
Anilides/pharmacology , Histamine H1 Antagonists/pharmacology , Anaphylaxis/drug therapy , Anilides/therapeutic use , Anilides/toxicity , Animals , Anti-Inflammatory Agents/pharmacology , Antigen-Antibody Reactions/drug effects , Cromolyn Sodium/pharmacology , Dogs , Histamine H1 Antagonists/therapeutic use , Histamine H1 Antagonists/toxicity , Histamine Release/drug effects , Immunosuppressive Agents/pharmacology , Lung/metabolism , Male , Mast Cells/metabolism , Mice , Passive Cutaneous Anaphylaxis/drug effects , RatsABSTRACT
Pretreatment with AMPT at doses which markedly altered the self-injection or amphetamine did not affect the self-injection of apomorphine. These data support the idea that the self-injection of apomorphine is produced via the direct activation of dopamine receptors rather than by the release of either norepinephrine or dopamine.
Subject(s)
Apomorphine/administration & dosage , Conditioning, Operant/drug effects , Dopamine , Methyltyrosines/pharmacology , Receptors, Drug/drug effects , Reward , Amphetamine/administration & dosage , Animals , Female , Rats , Reinforcement Schedule , Time FactorsABSTRACT
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.
Subject(s)
Immunity/drug effects , Meperidine/analogs & derivatives , Anaphylaxis/drug therapy , Animals , Carbamates/pharmacology , Cromolyn Sodium/pharmacology , Histamine Release/drug effects , Lung/drug effects , Male , Mast Cells/drug effects , Meperidine/pharmacology , Passive Cutaneous Anaphylaxis/drug effects , Peritoneum/metabolism , Rats , Skin/drug effects , Time FactorsABSTRACT
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.