Abstract: The present invention is directed to the production of PKC isozyme ? (PKC?)-deficient cells and non-human animals. The present invention is further directed to the identification of PKC? as a target for drugs that reduce anxiety. According to the present invention, PKC?-inhibiting compounds act in synergy with drugs acting at the GABAA receptor. The present invention is also directed to the use of modulators of PKC? 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?, either alone or in conjunction with allosteric agonists of GABAA 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.

Abstract: The present invention provides a method of reducing or preventing a drug-related effect or behavior in a subject by inhibiting N-type calcium channels. In addition, the invention provides a variety of prescreening and screening methods aimed at identifying agents that modulate a drug-related effect or behavior. These methods involve assaying test agent binding to N-type calcium channels or channel subunits. Alternatively, test agents can be screened for their ability to alter the level of N-type calcium channels, channel subunit polypeptide or RNA, or the depolarization-induced inward calcium current mediated by these channels. Finally, the invention also provides a diagnostic method that entails measuring one or more of these levels and determining risk for a drug-related effect or behavior based on comparison to the corresponding level for a control population.

Abstract: The present invention provides a method of reducing or preventing a drug-related effect or behavior in a subject by inhibiting N-type calcium channels. In addition, the invention provides a variety of prescreening and screening methods aimed at identifying agents that modulate a drug-related effect or behavior. These methods involve assaying test agent binding to N-type calcium channels or channel subunits. Alternatively, test agents can be screened for their ability to alter the level of N-type calcium channels, channel subunit polypeptide or RNA, or the depolarization-induced inward calcium current mediated by these channels. Finally, the invention also provides a diagnostic method that entails measuring one or more of these levels and determining risk for a drug-related effect or behavior based on comparison to the corresponding level for a control population.

Abstract: The present invention is directed to the production of PKC isozyme &egr; (PKC&egr;)-deficient cells and non-human animals. The present invention is further directed to the identification of PKC&egr; as a target for drugs that reduce anxiety. According to the present invention, PKC&egr;-inhibiting compounds act in synergy with drugs acting at the GABAA receptor. The present invention is also directed to the use of modulators of PKC&egr; 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&egr;, either alone or in conjunction with allosteric agonists of GABAA 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.

Abstract: The role of the E isozyme of protein kinase C (“PKC&egr;”) in pain perception, particularly hyperalgesia, methods of lessening pain through administration of inhibitors of PKC&egr;, methods of identifying compounds that modulate pain, and pharmaceutical compositions comprising an inhibitor of PKC&egr; and PKC&egr;-independent analgesic agent are disclosed.

Abstract: The present invention is directed to the production of PKC isozyme &egr; (PKC&egr;)-deficient cells and non-human animals. The present invention is further directed to the identification of PKC&egr; as a target for drugs that reduce anxiety. According to the present invention, PKC&egr;-inhibiting compounds act in synergy with drugs acting at the GABAA receptor. The present invention is also directed to the use of modulators of PKC&egr; 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&egr;, either alone or in conjunction with allosteric agonists of GABAA 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.

Abstract: The role of the &egr; isozyme of protein kinase C (“PKC&egr;”) in pain perception, particularly hyperalgesia, methods of lessening pain through administration of inhibitors of PKC&egr;, methods of identifying compounds that modulate pain, and pharmaceutical compositions comprising an inhibitor of PKC&egr; and PKC&egr;-independent analgesic agent are disclosed.

Abstract: This invention pertains to the discovery of a novel pathway that mediates hyperalgesia, neuropathic pain, and inflammatory pain. This pathway is a third independent pathway that involves activation of extracellular signal-regulated kinases (ERKs) 1 and 2. The pathway comprises a Ras-MEK-ERK1/2 cascade that acts independent of PKA or PKC&egr; as a novel signaling pathway for the production of inflammatory (and neuropathic) pain. This pathway presents numerous targets for a new class of analgesic agents.

Abstract: The role of the &egr; isozyme of protein kinase C (“PKC&egr;”) in pain perception, particularly hyperalgesia, methods of lessening pain through administration of inhibitors of PKC&egr;, methods of identifying compounds that modulate pain, and pharmaceutical compositions comprising an inhibitor of PKC&egr; and PKC&egr;-independent analgesic agent are disclosed.

Abstract: The present invention is directed to the production of PKC isozyme &egr; (PKC&egr;)-deficient cells and non-human animals. The present invention is further directed to the identification of PKC&egr; as a target for drugs that reduce anxiety. According to the present invention, PKC&egr;-inhibiting compounds act in synergy with drugs acting at the GABAA receptor. The present invention is also directed to the use of modulators of PKC&egr; 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&egr;, either alone or in conjunction with allosteric agonists of GABAA 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.

Abstract: The role of the &egr; isozyme of protein kinase C (“PKC&egr;”) in pain perception, particularly hyperalgesia, methods of lessening pain through administration of inhibitors of PKC&egr;, methods of identifying compounds that modulate pain, and pharmaceutical compositions comprising an inhibitor of PKC&egr; and PKC&egr;-independent analgesic agent are disclosed.