Effect of picumast dihydrochloride on antigen-induced early and late airway responses in allergic sheep. 1989

W M Abraham
Department of Research, Mount Sinai Medical Center, Miami Beach, FL.

In this study the effects of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) a novel antiallergic agent, on antigen-induced early and late responses in allergic sheep were examined. For all studies picumast dihydrochloride was administered as an aerosol approximately 20 min before airway challenge with Ascaris suum antigen. Allergic sheep were challenged on four occasions each greater than or equal to 14 days apart: one placebo trial and after 1 mg, 2.5 mg, and 5 mg picumast dihydrochloride aerosol (total dose nebulized). Specific lung resistance (SRL) was used as an index of the airway response to antigen and was measured before and serially after antigen challenge. In the placebo trial (n = 11) antigen challenge resulted in significant early and late airway responses (i.e. 382% and 185% increases in SRL, respectively). Picumast dihydrochloride at 1.0 mg (n = 7) did not protect against the antigen-induced increases in SRL. At 2.5 mg (n = 7), picumast dihydrochloride gave 48% and 55% (both p less than 0.05) protection against the early and late airway responses, respectively. These effects were slightly enhanced with 5 mg picumast dihydrochloride (n = 7) giving 63% protection against the early response and 81% against the late response. These results suggest that the antiallergic agent picumast dihydrochloride may provide some benefit in the treatment of allergic airway disease.

UI MeSH Term Description Entries
D006967 Hypersensitivity Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. Allergy,Allergic Reaction,Allergic Reactions,Allergies,Hypersensitivities,Reaction, Allergic,Reactions, Allergic
D007275 Injections, Intravenous Injections made into a vein for therapeutic or experimental purposes. Intravenous Injections,Injection, Intravenous,Intravenous Injection
D012137 Respiratory System The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. Respiratory Tract,Respiratory Systems,Respiratory Tracts,System, Respiratory,Tract, Respiratory
D003374 Coumarins Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid. 1,2-Benzopyrone Derivatives,1,2-Benzopyrones,Coumarin Derivative,Coumarine,1,2-Benzo-Pyrones,Benzopyran-2-ones,Coumarin Derivatives,Coumarines,1,2 Benzo Pyrones,1,2 Benzopyrone Derivatives,1,2 Benzopyrones,Benzopyran 2 ones,Derivative, Coumarin,Derivatives, 1,2-Benzopyrone,Derivatives, Coumarin
D006634 Histamine H1 Antagonists Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000336 Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. Aerosol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000941 Antigens Substances that are recognized by the immune system and induce an immune reaction. Antigen
D001200 Ascaris A genus of nematodes of the superfamily ASCARIDOIDEA whose species usually inhabit the intestine. Ascari

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