Abstract: A method for alleviating or delaying onset of pain in a subject via administration of an ultra low dose of alpha-2 receptor antagonist which does not significantly block or inhibit alpha-2 receptor activity is provided. A non-selective alpha-2 receptor antagonist or a selective alpha-2A receptor antagonist may be administered.

Abstract: Combination therapies of an opioid receptor agonist and a cannabinoid receptor antagonist in an amount effective to potentiate a therapeutic activity of the opioid receptor agonist and/or inhibit, delay, reduce and/or reverse tolerance to the opioid receptor agonist are provided. Also provided are methods for use of these combination therapies in potentiating a therapeutic activity of an opioid receptor agonist and/or inhibiting, delaying or reducing development of acute and/or chronic tolerance to opioid receptor agonists and treating conditions treatable by opioid receptor agonist therapy in a subject. In addition, a method for reversing opioid receptor agonist tolerance and/or restoring therapeutic effect of an opioid receptor agonist in a subject via administration of a cannabinoid receptor antagonist is provided.

Abstract: Combination therapies of an alpha-2 adrenergic receptor agonist and an alpha-2 adrenergic receptor antagonist at a concentration effective to potentiate but not antagonize a therapeutic effect of the alpha-2 adrenergic receptor agonist are provided. Also provided are methods for use of these combination therapies in potentiating the therapeutic effects of alpha-2 adrenergic receptor agonists, inhibiting development of acute and/or chronic tolerance to alpha-2 adrenergic receptor agonists and treating conditions treatable by alpha-2 adrenergic receptor agonist therapy in a subject. In addition, a method for reversing alpha-2 adrenergic receptor agonist tolerance and/or restoring therapeutic effect of an alpha-2 adrenergic receptor agonist in a subject via administration of an alpha-2 adrenergic receptor antagonist at a concentration effective to potentiate, but not antagonize, the therapeutic effect of the alpha-2 adrenergic receptor agonist is provided.

Abstract: Methods and therapeutic compounds for treating pain, mitigating inflammation, effecting analgesia and/or effecting sedation in a subject are described. A subject is administered an effective amount of a therapeutic compound which is a nitrate ester. Novel pharmaceutical compositions are also described.

Abstract: Combination therapies of an opioid receptor agonist and an alpha-2 receptor antagonist in an amount effective to potentiate, but not antagonize, a therapeutic effect of the opioid receptor agonist are provided. Also provided are methods for use of these combination therapies in potentiating the therapeutic effects of opioid receptor agonists, inhibiting development of acute and/or chronic tolerance to opioid receptor agonists and treating conditions treatable by opioid receptor agonist therapy in a subject. In addition, a method for reversing opioid receptor agonist tolerance and/or restoring therapeutic effect of an opioid receptor agonist in a subject via administration of an alpha-2 receptor antagonist in an amount effective to potentiate, but not antagonize, the therapeutic effect of the opioid receptor agonist is provided.

Abstract: Methods and therapeutic compounds for treating pain, mitigating inflammation, effecting analgesia and/or effecting sedation in a subject are described. A subject is administered an effective amount of a therapeutic compound which is a nitrate ester. Novel pharmaceutical compositions are also described.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Nitrate esters and methods for mitigating neurodegeneration, affecting neuroprotection, affecting cognition enhancement, and/or preventing or mitigating tissue and/or cellular damage in a subject are described. Neurological or cognitive conditions, or damage mediated by free radicals are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt thereof.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Compounds and methods for mitigating neurodegeneration, effecting neuroprotection and/or effecting cognition enhancement in a subject are described. Neurological or cognitive conditions are treated by administering to a subject an effective amount of a therapeutic compound comprising a nitrate ester, or a pharmaceutically acceptable salt or ester thereof.

Abstract: Aliphatic nitrate esters having a sulfur or phosphorus atom .beta. or .gamma. to a nitrate group and their congeners having efficacy as neuroprotective agents are described. Preferred nitrate esters may be synthesized by nitration of a 3-bromo-1,2-propanediol, and subsequent reaction to yield the desired mono-, di- or tetra-nitrate ester.