Abstract: The agrin protein was shown to be important in preventing the development of neuropathic pain, as well as in treating neuropathic pain. Both agrin protein and gene expression were shown to be down-regulated in mammals with neuropathic pain. Increasing either agrin gene expression or protein resulted in a decrease in the development of neuropathic pain. Agrin protein or the C-terminal agrin fragments can be administered in a number of ways, preferably by intrathecal injection. In addition, agrin can be increased by administering a compound shown to affect agrin gene expression or agrin protein concentration, e.g., SCP-I and SCP-M1 (also known as JMM). Agrin protein decrease was shown to be prevented by administering an NMDA receptor antagonist, e.g., MK801. Agrin and a C-terminal agrin fragment also induced phosphorylation of the NMDA receptor subunit NR1 at the serine residue site which led to suppression of neuropathic pain.

Abstract: The present invention relates to pharmaceutical combinations of opioid and non-opioid analgesics in an intimate admixture with caffeine and an analgesic from a series of N-acylated 4-hydroxyphenylamine derivatives, linked via an alkylene bridge to the nitrogen atom of a 1,2-benzisothiazol-3(2H)-one 1,1-dioxide group and methods for their use to alleviate pain in mammals. The analgesic combinations exhibit enhanced analgesic potency and are free from antipyretic activity, do not suppress blood coagulation, and have little hepatotoxic effect.

Abstract: The present invention relates to pharmaceutical combinations of opioid and non-opioid analgesics in an intimate admixture with an analgesic from a series of N-acylated 4-hydroxyphenylamine derivatives, linked via an alkylene bridge to the nitrogen atom of a 1,2-benzisothiazol-3(2H)-one 1,1-dioxide group and methods for their use to alleviate pain in mammals. The analgesic combinations exhibit enhanced analgesic potency, do not suppress blood coagulation, and have little hepatotoxic effect.

Abstract: The present invention relates to pharmaceutical combinations of opioid and non-opioid analgesics in an intimate admixture with caffeine and an analgesic from a series of N-acylated 4-hydroxyphenylamine derivatives, linked via an alkylene bridge to the nitrogen atom of a 1,2-benzisothiazol-3(2H)-one 1,1-dioxide group and methods for their use to alleviate pain in mammals. The analgesic combinations exhibit enhanced analgesic potency and are free from antipyretic activity, do not suppress blood coagulation, and have little hepatotoxic effect.

Abstract: New analgesic compounds, which are prepared by the hydrolysis of N-acylated 4-hydroxyphenylamine derivatives, their synthesis and pharmaceutical compositions containing them are disclosed. These compounds surprisingly possess high analgesic activity with little hepatotoxic effect, making them more useful than conventional non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of chronic pain.

Abstract: The present invention includes the characterization of the DGKe gene and the generation of screening methods for compounds that inhibit the function of DGKe. The DGK family of enzymes occupies a signaling crossroads since they catalyze the phosphorylation of DAG to produce PA. Both the substrate (DAG) and the product (PA) of this reaction are key factors in intracellular signaling, making the regulation of DGKe activity important to understand and control. DGKe −/− mice were also generated and studied to assist in understanding the function of DGKs in regulating cellular signaling. DGKe displays selectively for 20:4-DAG and is highly expressed in different areas of the brain, including Purkinje cells in the cerebellum, hippocampal interneurons, and the Pyramidal neurons in the CA3 region of the hippocampus.

Abstract: The present invention relates to pharmaceutical combinations of opioid and non-opioid analgesics in an intimate admixture with an analgesic from a series of N-acylated 4-hydroxyphenylamine derivatives, linked via an alkylene bridge to the nitrogen atom of a 1,2-benzisothiazol-3(2H)-one 1,1-dioxide group and methods for their use to alleviate pain in mammals. The analgesic combinations exhibit enhanced analgesic potency and are free from antipyretic activity, do not suppress blood coagulation, and have little hepatotoxic effect.

Abstract: The present invention relates to a series of new N-acylated 4-hydroxyphenylamine derivatives, linked via an alkylene bridge to the nitrogen atom of a 1,2-benzisothiazol-3(2H)-one 1,1-dioxide group of formula I: ##STR1## in which n is a number from 1 to 5, and to processes for preparing these derivatives and to pharmaceutical compositions containing said derivatives; these compounds possess high analgesic activity free from antipyretic activity, and they display little hepatotoxic effect.

Abstract: The present invention relates to a series of new N-acylated 4-hydroxyphenylamine derivatives, linked via an alkylene bridge to the nitrogen atom of a 1,2-benzisothiazol-3(2H)-one 1,1-dioxide group, of formula I: ##STR1## in which n is a number from 1 to 5, and to processes for preparing these derivatives and to pharmaceutical compositions containing said derivatives; these compounds possess high analgesic activity free from antipyretic activity, and they display little hepatotoxic effect.