Abstract: In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.

Abstract: In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.

Abstract: In alternative embodiments, the provided are therapeutic combinations comprising: nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nervous system (CNS); and, a brain efflux transporter inhibitor, or an inhibitor of renal tubular secretion, wherein optionally the brain efflux transporter inhibitor or the inhibitor of renal tubular secretion comprises a P-glycoprotein inhibitor, an organic anion transporter (OAT) inhibitor and/or an organic cation (OCT) transporter inhibitor.

Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.

Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.

Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.

Abstract: In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (?7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (?7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”).

Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.

Abstract: Provided are N-alkyl imidazole 2-aldoximes, including cationic imidazolium and uncharged tertiary imidazole aldoximes, and compositions and methods for making and using them, including methods for reactivating human butyrylcholinesterase (hBChE) or acetylcholinesterase (hAChE) inhibited by organophosphate (OP). By administration of a composition of the invention, the inactive or conjugated hBChE-OP or hAChE-OP is reactivated and the catalytic cycle of turnover and inactivation of the OP is completed; and in alternative embodiments, secondary mechanisms of reversible protection of hBChE and hAChE from irreversible inactivation by OPs and reactivation of tissue AChE also contribute to overall efficacy.

Abstract: In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (?7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (?7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”).

Abstract: Provided are N-alkyl imidazole 2-aldoximes, including cationic imidazolium and uncharged tertiary imidazole aldoximes, and compositions and methods for making and using them, including methods for reactivating human butyrylcholinesterase (hBChE) or acetylcholinesterase (hAChE) inhibited by organophosphate (OP). By administration of a composition of the invention, the inactive or conjugated hBChE-OP or hAChE-OP is reactivated and the catalytic cycle of turnover and inactivation of the OP is completed; and in alternative embodiments, secondary mechanisms of reversible protection of hBChE and hAChE from irreversible inactivation by OPs and reactivation of tissue AChE also contribute to overall efficacy.

Abstract: In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps.

Abstract: Disclosed are methods for the preparation and use of labeled AChE and labeled AChE inhibitory conjugate compositions for detecting accumulation of toxic materials such as organophosphates, insecticides, and other nerve agents. Also disclosed are methods for the use of labeled AChE and labeled AChE inhibitory conjugate compositions in a variety of areas, including the detecting of toxic materials in biological samples, in the area of food and water analysis, in environmental monitoring, and in industrial settings.

Abstract: Provided are methods and compositions for treating autism spectrum disorders by administering an antioxidant or agent that stabilize or enhance expression of altered neuroligins. An aspect of the disclosure includes site-specific delivery of the antioxidant to the endoplasmic reticulum (ER) to reverse incorrect disulfide binding of the protein neuroligin. Also disclosed is a method of targeting the antioxidant to neuroligin by using the calcium binding or other recognition site of neuroligin to bind the antioxidant. The antioxidant can be cysteamine linked to a molecule which binds to a binding site.

Abstract: Fluorescence based screening assays are provided that allow for the for identification of agents that selectively bind to a ligand-gated ion channel (LGIC) such as a nicotinic acetylcholine receptor (nAChR). Also provided are methods for identifying agents that selectively bind to a neuronal-type nAChR by detecting binding of the agent to an Aplysia AChBP, which is representative of a neuronal-type nAChR. In addition, compositions and kits for performing such methods are provided.

Abstract: Provided are methods and compositions for treating autism spectrum disorders by administering an antioxidant or agent that stabilize or enhance expression of altered neuroligins. An aspect of the disclosure includes site-specific delivery of the antioxidant to the endoplasmic reticulum (ER) to reverse incorrect disulfide binding of the protein neuroligin. Also disclosed is a method of targeting the antioxidant to neuroligin by using the calcium binding or other recognition site of neuroligin to bind the antioxidant. The antioxidant can be cysteamine linked to a molecule which binds to a binding site.

Abstract: Fluorescence based screening assays are provided that allow for the for identification of agents that selectively bind to a ligand-gated ion channel (LGIC) such as a nicotinic acetylcholine receptor (nAChR). Also provided are methods for identifying agents that selectively bind to a neuronal-type nAChR by detecting binding of the agent to an Aplysia AChBP, which is representative of a neuronal-type nAChR. In addition, compositions and kits for performing such methods are provided.

Abstract: Disclosed are methods for the preparation and use of labeled AChE and labeled AChE inhibitory conjugate compositions for detecting accumulation of toxic materials such as organophosphates, insecticides, and other nerve agents. Also disclosed are methods for the use of labeled AChE and labeled AChE inhibitory conjugate compositions in a variety of areas, including the detecting of toxic materials in biological samples, in the area of food and water analysis, in environmental monitoring, and in industrial settings.

Abstract: A method of detoxifying organophosphates using mutant cholinesterase which esists aging. The addition of oximes to the cholinesterase further retards aging of the cholinesterase.