Biomaterial Database

In vivo pharmacology of ICI 198,615: a novel, potent and selective peptide leukotriene antagonist. 1987

R D Krell, and R E Giles, and Y K Yee, and D W Snyder

Department of Pharmacology, Stuart Pharmaceuticals, Division of ICI Americas Inc., Wilmington, Delaware.

The in vivo pharmacology of ICI 198,615, a highly potent and selective peptide leukotriene (LT) receptor antagonist, is described. In a conscious guinea pig model, ICI 198,615 provided dose-related antagonism of aerosol LTD4-induced dyspnea when administered p.o., i.v. or by aerosol. The pharmacologic half-lives of ICI 198,615 by these routes of administration were greater than 16 hr, 68 min and 34 min, respectively. In pulmonary mechanics studies in which the effects of i.v. or aerosol administration of LTC4 and LTD4 on pulmonary resistance (Rp) or dynamic lung compliance (Cdyn) could be quantitated, ICI 198,615 provided dose-related antagonism when administered p.o., i.d, i.v. or by aerosol. The compound also antagonized LTE4-induced changes in Rp and Cdyn when administered i.v. ICI 198,615 reversed the effect of LTC4, LTD4 and LTE4 on Rp, as well as the effect of LTC4 and LTE4 on Cdyn. The compound was less able to reverse the effect of LTD4 on Cdyn. These results indicate that ICI 198,615 possesses an in vivo profile which is consonant with utility in the treatment of allergic diseases.

UI	MeSH Term	Description	Entries
D007191	Indazoles	A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.	Indazole
D007275	Injections, Intravenous	Injections made into a vein for therapeutic or experimental purposes.	Intravenous Injections,Injection, Intravenous,Intravenous Injection
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D011982	Receptors, Prostaglandin	Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).	Prostaglandin Receptors,Prostaglandin Receptor,Receptor, Prostaglandin,Receptors, Prostaglandins,Prostaglandins Receptors
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
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