The United States of America As Represented by the Department of Health

G.d. Searle & Company

National Institutes of Health

Thomas L O'Donohue

Kenner C Rice

Arthur E Jacobson

Patricia C Contreras

Mariena V Mattson

Andrew Y Thurkauf

Michael Francis Rafferty

Nancy M Gray

Ralph A Lessor

Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of an N-(1-thienylcycloalkyl)alkenylamine compound as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula ##STR1## wherein R.sup.1 is one or more groups selected from hydrido, alkyl of one to about five carbon atoms, cycloalkyl of three to about five carbon atoms, alkenyl of two to about five carbon atoms, hydroxyl and alkoxy; wherein each of R.sup.2 is one or more groups selected from hydrido, alkyl of one to about five carbon atoms, cycloalkyl of three to about five carbon atoms, alkenyl of two to about five carbon atoms, hydroxyl, oxo and alkoxy; wherein R.sup.5 is one or more groups selected from hydrido, alkyl of one to about five carbon atoms, cycloalkyl of three to about five carbon atoms, alkenyl of two to about five carbon atoms, hydroxyl and alkoxy; and wherein the broken line within the N-containing ring represents a double bond between any two adjacent carbon atoms

N-(1-thienylcycloalkyl)alkenylamines for treatment of neurotoxic injury

Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of an N-(1-thienylcycloalkyl)alkenylamine compound as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula ##STR1## wherein R.sup.1, R.sup.2, and R.sup.5 are defined in specification.

A derivative of phencyclidine (1) bearing an isothiocyanate moiety on the meta position of the aromatic ring (3; Metaphit as methanesulfonate and HCl salt) has been synthesized and identified as a rapid and specific site-directed acylating agent of the [.sup.3 H]-phencyclidine binding site in rat brain homogenates. Additional related compounds to Metaphit are Thiophit (oxalate salt), Ethylphit (HCl salt), and Isopropylphit (HCl salt).

Metaphit and related compounds as acylating agents for the

A derivative of phencyclidine (1) bearing an isothiocyanate moiety of the meta position of the aromatic ring (2; Metaphit) has been synthesized and identified as a rapid and specific site-directed acylating agent of the [.sup.3 H]-phencyclidine binding site in rat brain homogenates.

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Chesterfield, MO, United States of America

Thomas L O'Donohue