The present invention is directed to the production of PKC isozyme .epsilon. (PKC.epsilon.)-deficient cells and non-human animals. The present invention is further directed to the identification of PKC.epsilon. as a target for drugs that reduce anxiety. According to the present invention, PKC.epsilon.-inhibiting compounds act in synergy with drugs acting at the GABA.sub.A receptor. The present invention is also directed to the use of modulators of PKC.epsilon. to modulate alcohol consumption, self-administration of other drugs of abuse, and the effects of alcohol consumption as well as the use of inhibitors of PKC.epsilon., either alone or in conjunction with allosteric agonists of GABA.sub.A receptors, to treat conditions, such as addiction, withdrawal syndrome, skeletal muscle spasms, convulsive seizures, and epilepsy, that are amenable to treatment by allosteric agonists of GABA.sub.A receptors. Additional aspects of the present invention are diagnostic methods for identifying individuals at risk for becoming alcoholics or abusers of other drugs and kits for performing such diagnostic methods. The present invention relates to: cells and non-human animals deficient for the PKC isozyme .epsilon. (PKC.epsilon.); the use of PKC.epsilon. as a target for drugs; the use of inhibitors of PKC.epsilon. in methods of reducing anxiety and treating conditions associated with insufficient activity of the GABA.sub.A receptor; the use of modulators of PKC.epsilon. in methods of modulating alcohol consumption, modulating self-administration of other drugs of abuse, and altering the effects of alcohol; pharmaceutical compositions comprising inhibitors of PKC.epsilon. and allosteric agonists of GABA.sub.A receptors; and the identification of individuals with enhanced susceptibility to alcoholism or other forms of addiction.

The Regents of the University of California

Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse

The present invention is directed to the production of PKC isozyme .epsilon. (PKC.epsilon.)-deficient cells and non-human animals. The present invention is further directed to the identification of PKC.epsilon. as a target for drugs that reduce anxiety. According to the present invention, PKC.epsilon.-inhibiting compounds act in synergy with drugs acting at the GABA.sub.A receptor. The present invention is also directed to the use of modulators of PKC.epsilon. to modulate alcohol consumption, self-administration of other drugs of abuse, and the effects of alcohol consumption as well as the use of inhibitors of PKC.epsilon., either alone or in conjunction with allosteric agonists of GABA.sub.A receptors, to treat conditions, such as addiction, withdrawal syndrome, skeletal muscle spasms, convulsive seizures, and epilepsy, that are amenable to treatment by allosteric agonists of GABAA receptors. Additional aspects of the present invention are diagnostic methods for identifying individuals at risk for becoming alcoholics or abusers of other drugs and kits for performing such diagnostic methods. The present invention relates to: cells and non-human animals deficient for the PKC isozyme .epsilon. (PKC.epsilon.; the use of PKC.epsilon. as a target for drugs; the use of inhibitors of PKC.epsilon. in methods of reducing anxiety and treating conditions associated with insufficient activity of the GABA.sub.A receptor; the use of modulators of PKC.epsilon. in methods of modulating alcohol consumption, modulating self-administration of other drugs of abuse, and altering the effects of alcohol; pharmaceutical compositions comprising inhibitors of PKC.epsilon. and allosteric agonists of GABA.sub.A receptors; and the identification of individuals with enhanced susceptibility to alcoholism or other forms of addiction.

Administration of a salt of bi-cyclo [2.2.2] octane-2-carbonic acid reduces dysphoria in dysphoric subjects, ameliorates ethanol craving in alcoholics, reduces the erythrocyte sedimentation rate and the level of liver function markers (AST, ALT, and bilirubin) in human subjects, and reduces the number or strength of seizures in epileptics.

ASE PHARMACEUTICALS, LLC

ASE Pharmaceuticals, LLC

[2.2.2] bicyclic derivatives and methods of use

Improving the antioxidant capacity in an animal by increasing the level of glutathione in the blood or tissue of the animal comprising providing a composition containing beta-casein to the animal for consumption, where the beta-casein comprises at least 75% by weight of one or more beta-caseins not capable of producing beta-casomorphin-7 on enzymatic digestion. Uses include as an oxidant, for treating or preventing the symptoms of cancer, inflammation, kwashiorkor (protein deficiency), seizure, autism, Down's syndrome, chronic fatigue syndrome, Alzheimer's disease, Parkinson's disease, sickle cell anaemia, liver disease, cystic fibrosis, HIV, AIDS, infection, heart attack, stroke, and diabetes, avoiding or reducing the effects of aging, promoting the recovery of tissue following physical exercise, and promoting fertility.

non-alcoholic fatty liver disease/seizures

Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse

Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse

[2.2.2] bicyclic derivatives and methods of use

Beta-casein A2 and antioxidant capacity

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