Pharmaceutical compositions and their methods of use
AssigneeAbbott Laboratories
InventorsMurali Gopalakrishnan, Marie P. Honore, Chih-Hung Lee, John Malysz, Jianguo Ji, Tao Li, Michael R. Schrimpf, Kevin B. Sippy, David J. Anderson
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Abstract
The invention relates to a composition comprising a neuronal nicotinic receptor ligand and an α4β2 positive allosteric modulator, a method of using the same, and a related article of manufacture.
Claims24
A composition, comprising:
- (i) a nicotinic acetylcholine receptor ligand and
- (ii) a nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator in admixture with at least one pharmaceutically acceptable excipient.
A method for use in treating or preventing pain in a patient, comprising:
- (i) administering an amount of nicotinic subtype α4β2 positive allosteric modulator to the patient;
- and
- (ii) administering a pain medication comprising a compound selected from an opioid, gabapentin, pregabalin, duloxetine, a cannabinoid ligand, a vaniolloid receptor antagonist, calcium channel blocker and a sodium channel blocker wherein a descending modulatory pathway that is shared or commonly activated via the α4β2 nicotinic receptor mechanism is activated.
A method for use in treating or preventing pain, including neuropathic pain and cognitive disorders in a patient, comprising:
- (i) administering an amount of nicotinic acetylcholine receptor ligand to the patient;
- and
- (ii) administering an amount of nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator to the patient;
- wherein the amounts of (i) and (ii) together are more effective in treating pain or cognitive disorders.
A method for use in treating or preventing a condition or disorder selected from attention deficit disorder, attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), substance abuse including alcohol abuse, bipolar disorder, mild cognitive impairment, age-associated memory impairment (AAMI), senile dementia, AIDS dementia, Pick's Disease, dementia associated with Lewy bodies, dementia associated with Down's syndrome, schizophrenia, schizoaffective disorder, smoking cessation, amyotrophic lateral sclerosis, Huntington's disease, diminished CNS function associated with traumatic brain injury, infertility, lack of circulation, need for new blood vessel growth associated with wound healing, ischemia, sepsis, inflammation and inflammatory disorders comprising:
- (i) administering an amount of nicotinic acetylcholine receptor ligand to the patient;
- and
- (ii) administering an amount of nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator to the patient;
- wherein the amounts of (i) and (ii) together are more effective in treating disorders.
A method for use of treating or preventing a condition or disorder characterized by attention or cognitive dysfunction comprising administering a therapeutically effective amount of a nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator to a subject in need thereof in combination with a nicotinic acetylcholine receptor ligand or an acetylcholinesterase inhibitor.
A method of treating or preventing a condition or disorder characterized by neuropsychological dysfunction comprising administering a therapeutically effective amount of a nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator to a subject in need thereof in combination with an antipsychotic agent.
An article of manufacture, comprising:
- (i) a first pharmaceutical dosage form comprising at least one nicotinic acetylcholine receptor ligand;
- and
- (ii) a second pharmaceutical dosage form comprising at least nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulator;
- wherein the article contains first and second pharmaceutical dosage forms.
A compound of formula:
- or a salt thereof, wherein Ar2 is substituted pyridinyl, unsubstituted pyridinyl, or substituted phenyl;
- and Ar3 is substituted pyridinyl, unsubstituted pyridinyl, or substituted phenyl;
- wherein the pyridinyl group, when substituted, is substituted with fluoro and the phenyl group is substituted with cyano, sulfonamide or fluoro.
A compound of formula:
- or a salt thereof, wherein
- Ar2 is monocyclic aryl or monocyclic heteroaryl, wherein the aryl or heteroaryl is substituted or unsubstituted, and, when substituted, the aryl or heteroaryl is substituted with 1, 2, 3, or 4 substituents selected from halo, C1-C6 haloalkyl, C6-C10 aryl, C4-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C5-C10 heteroaryl, C4-C10 heterocycle, C1-C6 alkyl, —(C1-C6 alkyl)NHC(O)O—(C1-C6 alkyl), C1-C6 hydroxyalkyl, C1-C6 alkylcarbonyl, amino, hydroxyl, haloalkyl-C(O)—, haloalkyl-SO2—, alkyl-SO2—, —SO2NH2, —SO2NH(C1-C6 alkyl), —SO2N(C1-C6 alkyl)2, cyano, nitro, C1-C6 acylamino, C1-C6 alkoxy, —C(O)NH2, —C(O)O—(C1-C6 alkyl), and carboxy;
- and
- Ar3 is monocyclic aryl or monocyclic heteroaryl, wherein the aryl or heteroaryl is substituted or unsubstituted, and, when substituted, the aryl or heteroaryl is substituted with a substituent selected from halo, C1-C6 haloalkyl, C6-C10 aryl, C4-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C5-C10 heteroaryl, C1-C6 alkyl, C1-C6 hydroxyalkyl, amino, hydroxyl, haloalkyl-SO2—, cyano, nitro, C1-C6 acylamino, C1-C6 alkoxy, —N(C1-C6 alkyl)2, and carboxy;
- wherein at least one of the available atoms within a compound of formula (II*) is replaced with a radioisotope.
A compound that is [3H]-3-(5-(pyridin-3-yl)-1,2,4-oxadiazol-3-yl)benzonitrile.
Use of a radiolabelled form of a compound of formula (II*) for determining the binding affinity of nicotinic acetylcholine receptor subtype α4β2 positive allosteric modulators.
Dependencies are inferred from the claim text.