Neurex Corporation

Elan Pharmaceuticals, Inc.

Stephen S Bowersox

George P Miljanich

Robert S Bitner

Karen L Valentino

James A Fox

Donald H Yamashiro

Laszlo Nadasdi

Roberto Crea

Jack D Barchas

Susan D Demo

Catherine M Bitler

Balazs G Szoke

Laszlo Urge

Robert W Newcomb

Gary Arthur Amstutz

William A Horne

Katalin Tarczy-Hornoch

Mei Zhou

Glen R Elliott

Andrew L Palma

Peter I Adriaenssens

Ruth L Cong

Robin Dean

Makoto Tsubokawa

Kishorchandra Gohil

William F Hopkins

Peter Isadore Adriaenssens

Ramasharma Kristipati

James L Miller

Theresa M Gadbois

Talmage Bosin

Victor C Yu

A novel class of peptides selectively block class E voltage-gated calcium channels. The class is exemplified by HG peptides such as HG-1, which is isolated from the venom-producing cells of the tarantula Hysterocrates gigas. Also disclosed are methods of producing blocking class E channels using the peptides. HG peptides have utility, for example, in inhibiting oxytocin release and for use as anticonvulsants.

Voltage-gated calcium channel antagonist and method

Disclosed is a method of selecting analgesic agents based on their selective ability to block tetrodotoxin-insensitive sodium channels, particularly in comparison to blocking tetrodotoxin-sensitive sodium channels. Also disclosed is a novel class of compounds that is selective for blocking tetrodotoxin-insensitive sodium channels.

Analgesic screening method and composition

Bax-.omega. polynucleotides and polypeptides, and compositions effective to hybridize to Bax-.omega. polynucleotides are disclosed. Also disclosed are methods for altering apoptosis in cells, for promoting cell survival and for identifying compounds capable of affecting the binding of Bax-.omega. to other proteins involved in apoptosis.

Bax .omega. protein and methods

A method of preventing progression of neuropathic pain is disclosed. The method includes administering to a subject an N-type voltage-sensitive calcium channel blocking compound which is characterized by its ability to (a) inhibit electrically stimulated contraction of the guinea pig ileum, and (b) bind selectively to omega conopeptide MVIIA binding sites present in neuronal tissue. Also disclosed are formulations effective to stabilize omega conotoxin peptide preparations at elevated temperatures. Novel omega conopeptides also form part of the invention.

Methods and formulations for preventing progression of neuropathic pain

Disclosed are formulations effective to stabilize omega conotoxin peptide preparations at elevated temperatures. Novel omega conopeptides also form part of the invention.

Stable omega conopetide formulations

Bax omega protein and methods

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.

Benzothiophenes as appetite suppressants

Growing community of inventors

Menlo Park, CA, United States of America

Stephen S Bowersox