Biomaterial Database

Histamine(H1) antagonists and airway hyperreactivity in the guinea-pig. 1991

K Hoshiko, and I D Chapman, and J Morley

Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.

Ketotifen inhibits development of airway hyperreactivity in guinea-pigs exposed to PAF, (+/-)isoprenaline, immune complexes or endotoxin. Ketotifen is not a competitive histamine(H1) antagonist, so that it cannot be concluded that there is mandatory involvement of histamine in the development or expression of these forms of airway hyperreactivity. This conclusion has been reinforced by determining the efficacy of other histamine(H1) antagonists as inhibitors of PAF-induced airway hyperreactivity. When compounds were administered intravenously, at a dosage (1 mg/kg) which fully abolished responses to intravenous histamine, the observed rank order for inhibition of PAF-induced hyperreactivity was: ketotifen greater than cetirizine greater than acrivastine greater than KB-2413 greater than oxatomide greater than azelastine greater than terfenadine = astemizole = clemastine = mepyramine = loratadine = saline. Terfenadine may lack inhibitory activity because of a capacity to induce airway hyperreactivity in the guinea-pig. It can be concluded that inhibition of the development of airway hyperreactivity is not a characteristic of histamine(H1) antagonists.

UI	MeSH Term	Description	Entries
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008297	Male		Males
D010972	Platelet Activating Factor	A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.	AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D012130	Respiratory Hypersensitivity	A form of hypersensitivity affecting the respiratory tract. It includes ASTHMA and RHINITIS, ALLERGIC, SEASONAL.	Airway Hyperresponsiveness,Hypersensitivity, Respiratory,Airway Hyper-Responsiveness,Airway Hyper Responsiveness,Airway Hyperresponsivenesses,Hyper-Responsiveness, Airway,Hyperresponsiveness, Airway,Respiratory Hypersensitivities
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006632	Histamine	An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.	Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
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
D000403	Airway Resistance	Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.	Airway Resistances,Resistance, Airway,Resistances, Airway
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
D016084	Bronchoconstriction	Narrowing of the caliber of the BRONCHI, physiologically or as a result of pharmacological intervention.	Bronchial Constriction,Bronchial Constrictions,Bronchoconstrictions,Constriction, Bronchial,Constrictions, Bronchial