Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Merck Sharpe & Dohme Corp.

Victor J Lotti

Graham A Showell

Raymond Baker

Ralph A Rivero

Steven M Pitzenberger

Sandor L Varga

Richard W Ransom

Peter K Siegl

Keith M Witherup

William J Lumma

Gloria J Zingaro

Salah Kivlighn

This invention relates to compounds represented by formula I: ##STR1## which are agonists of angiotensin II. The invention is also concerned with the use of aforementioned agonists in the treatment of states meditated by angiotensin.

Pharmaceutical treatment methods using angiotensin II receptor agonists

3(R)-[2-(6-trifluoromethylpyrazin)yl]-1-azabicyclo[2.2.2]octane and its salts, and pharmaceutical formulations thereof are useful in medicine. In particular, they are useful for the treatment of neurological and mental illnesses whose clinical manifestations are due to cholinergic deficiency, and for lowering intraocular pressure. The compound may be prepared by dehydroxylating or decarboxylating the corresponding 3-hydroxy- or carboxy-quinuclidine analogue.

Substituted pyrazine and its salts, compositions containing them and

A pyrroloquinoline compound of the following formula is disclosed: ##STR1## wherein H,

Pyrroloquinoline Bradykinin antagonist

A class of pyrazine, pyrimidine and pyridazine derivatives, substituted by a non-aromatic azabicyclic ring system and optionally by up to two further substituents, is of use in the preparation of medicaments, especially formulations adapted for topical administration to the eye, suitable for the treatment of glaucoma and/or for reducing intraocular pressure.

Substituted pyrazines, pyrimidines and pyridazines for use in the

Topical administration of a cholinomimetic agent, such as pilocarpine, in combination with a cholinergic M.sub.3 receptor antagonist, such as 4-diphenyl-acetoxy-N-methylpiperidine, to the eye of a mammal reduces intraocular pressure without the concommitant miotic effect that normally occurs with administration of a cholinomimetic agent along.

Method to reduce introacular pressure without causing miosis

The use of compounds for formula (I): ##STR1## or a salt or prodrug thereof; wherein one of X, Y, or Z is an oxygen or sulphur atom and the other two are nitrogen atoms, and the dotted circle represents two double bonds thus forming a 1,3,4-oxadiazole, 1,2,4-oxadiazole, 1,3,4-thiadiazole or 1,2,4-thiadiazole nucleus;

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Harleysville, PA, United States of America

Victor J Lotti