Abstract: The present invention provides methods of preventing and/or reducing risk of neurodegeneration of association cortex, and/or inhibiting or reversing formation of phosphorylated tau or COXIV in the prefrontal cortex of a mammal in need thereof. In certain embodiments, the method comprises administering to the mammal a therapeutically effective amount of an ?2A-adrenergic receptor agonist.

Abstract: The present invention provides methods of preventing and/or reducing risk of neurodegeneration of association cortex, and/or inhibiting or reversing formation of phosphorylated tau or COXIV in the prefrontal cortex of a mammal in need thereof. In certain embodiments, the method comprises administering to the mammal a therapeutically effective amount of an ?2A-adrenergic receptor agonist.

Abstract: Pseudobase benzo[c]phenanthridines and the pharmaceutically acceptable salts thereof of Formula I are provided herein. The variables R, R1, R2, R3, and R4 are defined herein. Certain pseudobase benzo[c]phenanthridines provided herein act as prodrugs, targeting the parent benzo[c]phenanthridinium alkaloid to hydrophilic or hydrophobic regions in the body. Pharmaceutical compositions comprising a pseudobase benzo[c]phenanthridine and a carrier, excipient, or diluent are provided herein. Methods of treating or preventing microbial, fungal and or viral infections and methods of treating diseases and disorders responsive to protein kinase C modulation, topoisomerase I, and/or topoisomerase II modulation are also provided.

Abstract: Pseudobase benzo[c]phenanthridines and the pharmaceutically acceptable salts thereof of Formula I are provided herein. The variables R, R1, R2, R3, and R4 are defined herein. Certain pseudobase benzo[c]phenanthridines provided herein act as prodrugs, targeting the parent benzo[c]phenanthridinium alkaloid to hydrophilic or hydrophobic regions in the body. Pharmaceutical compositions comprising a pseudobase benzo[c]phenanthridine and a carrier, excipient, or diluent are provided herein. Methods of treating or preventing microbial, fungal and or viral infections and methods of treating diseases and disorders responsive to protein kinase C modulation, topoisomerase I, and/or topoisomerase II modulation are also provided.

Abstract: Pseudobase benzo[c]phenanthridines and the pharmaceutically acceptable salts thereof of Formula I are provided herein. The variables R, R1, R2, R3, and R4 are defined herein. Certain pseudobase benzo[c]phenanthridines provided herein act as prodrugs, targeting the parent benzo[c]phenanthridinium alkaloid to hydrophilic or hydrophobic regions in the body. Pharmaceutical compositions comprising a pseudobase benzo[c]phenanthridine and a carrier, excipient, or diluent are provided herein. Methods of treating or preventing microbial, fungal and or viral infections and methods of treating diseases and disorders responsive to protein kinase C modulation, topoisomerase I, and/or topoisomerase II modulation are also provided.

Abstract: The present invention relates to the use of chelerythrine and chelerythrine analogs in pharmaceutical compositions for the treatment of prefrontal cortical cognitive disorders, including bipolar disorder, among others.

Abstract: The present invention relates to the use of inhibitors or blockers of Ih (hyperpolarization-activated cationic current) channels in the treatment of cognitive disorders.

Abstract: Aging is associated with deficiencies in the prefrontal cortex, including working memory impairment, and compromised integrity of neuronal dendrites. The role of Protein Kinase C(PKC) in age-related prefrontal cortical impairments had not been previously determined. The inventors provides evidence that PKC activity is associated with prefrontal cortical dysfunction in aging. The inventors provide methods of reversing the effects of prefrontal cortical decline, improving cognition, and improving working memory in aged subjects by providing a phenanthridinium alkaloid or closely related compound to the subject. The inventors found chelerythrine reversed working memory impairments in aged rats and enhanced working memory in aged rhesus monkeys. Improvement correlated with age, with older monkeys demonstrating a greater degree of improvement following PKC inhibition.

Abstract: Disclosed is a method of treating disorders which have prominent symptoms of behavioral disinhibition (e.g., Attention-Deficit Hyperactivity Disorder, Conduct Disorder, Oppositional Defiant Disorder, Tourette's Syndrome, Lesch-Nyhan Syndrome, or the disinhibitory symptoms accompanying Post-traumatic Stress Disorder or dementia) in a primate with minimal sedative side effects by administering thereto a therapeutically effective amount of lofexidine.

Abstract: Disclosed is a method of treating disorders which have prominent symptoms of behavioral disinhibition (e.g., Attention-Deficit Hyperactivity Disorder, Conduct Disorder, Oppositional Defiant Disorder, Tourette's Syndrome, Lesch-Nyhan Syndrome, or the disinhibitory symptoms accompanying Post-traumatic Stress Disorder or dementia) in a primate with minimal sedative side effects by administering thereto a therapeutically effective amount of guanfacine.

Abstract: Disclosed is a method of treating memory disorders and cognitive decline, e.g., age-related cognitive decline, in a primate by administering thereto a therapeutically effective amount of an alpha-2 agonist having a high affinity for the alpha-2I subtype, e.g., guanfacine and guanabenz or a nontoxic, pharmaceutically acceptable salt thereof. Particularly preferred is the use of alpha-2I selective agonists such as guanfacine.

Abstract: Disclosed is a method of treating cognitive decline in a normal aged primate by administering thereto a therapeutically effective amount of 2-[(2,6-dichlorophenyl)-amino]-2-imidazoline or a nontoxic, pharmaceutically acceptable salt thereof. Administration is preferably in amounts of at least about 0.001 mg/day.