Neurex Corporation

Robert S Bitner

Stephen S Bowersox

George P Miljanich

Karen L Valentino

James A Fox

Donald H Yamashiro

Jack D Barchas

Glen R Elliott

Peter I Adriaenssens

Makoto Tsubokawa

Laszlo Nadasdi

Theresa M Gadbois

Talmage Bosin

Victor C Yu

A method and compositions for reducing neuronal damage related to an ischemic condition in a mammalian subject are described. The method includes administration of a voltage-gated calcium channel-blocking compound to the subject, 4-24 hours after the onset of the ischemic condition. Such a calcium channel blocking compound is effective to block norepinephrine release in mammalian CNS neuronal cells and is characterized by specific, high affinity binding to omega-conotoxin MVIIA binding sites. Also disclosed are novel peptide structures useful in the treatment method of the invention.

Delayed treatment method of reducing ischemia-related neuronal damage

A partially purified omega conotoxin binding protein is disclosed. The protein, either in partially purified form or in a synaptosomal preparation, is useful in identifying compounds for use in reducing neuronal damage related to an ischemic condition, such as stroke, in a human patient.

Screening method for neuroprotective compounds

Method of reducing neuronal damage using omega conotoxin peptides

Compounds of formula I are useful for suppressing appetite, and for altering macronutrient preferences, ##STR1## where the R.sub.2 -R.sub.9 substituents are so selected as to meet a defined quantitative structure activity relationship (QSAR) quantity relating to the partition coefficient of the compound, the net charge on the ring nitrogen, and the radical superfdelocalizability at the position-8 ring carbon.

Method of suppressing appetite by administration of

A method of reducing neuronal damage related to an ischemic condition in a human patient, such as stroke-induced damage, by administration of a binding/inhibitory omega-conotoxin peptide.

Method of treating ischemia-related neuronal damage

Compounds of formula I are useful for suppressing appetite, for altering macronutrient preferences, for suppressing obsessive-compulsive behavior, and for inhibiting cravings and substance abuse: ##STR1## wherein R.sub.1 and R.sub.3 are each independently H, hydroxy-alkyl, alpha-cyanoalkyl, SO.sub.3 H, SO.sub.2 NH.sub.2, or C(O)R, where R is OH, NH.sub.2, lower alkoxy, benzyloxy, or aliphatic amino acyl;

Compositions comprising a compound of formula 1, and optionally a mild stimulant, are effective anorectics, where formula 1 is: ##STR1## and its pharmaceutically acceptable acid-addition salts, wherein X and Y are each independently hydrogen, hydroxy, methyl, ethyl, propyl, methoxy, ethoxy, propoxy, fluoro, chloro, or bromo. These compounds are effective for reducing appetite globally, or at lower dosage, for altering macronutrient preferences and decreasing substance dependence.

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Mountain View, CA, United States of America

Robert S Bitner