A comprehensive review of pharmacological and medical aspects of the muscarinic class of acetylcholine agonists and antagonists is presented. The therapeutic benefits of achieving receptor subtype selectivity are outlined and applications in the treatment of Alzheimer’s disease are discussed. A selection of chemical routes are described, which illustrate contemporary methodology for the synthesis of chiral medicinal compounds (asymmetric synthesis, chiral pool, enzymes). Routes to bicyclic intrannular amines and intramolecular Diels-Alder reactions are highlighted.

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Muscarinic Receptor Agonists and Antagonists

Methods and compositions for the treatment of pain. Particularly disclosed are new compositions for the treatment of chronic pain, and methods for their use.

Methods and compositions for modulating alpha adrenergic receptor activity

The present invention provides compounds of formula (I); pharmaceutical compositions thereof, and methods of using the same, processes or preparing the same, and intermediates thereof.

Potentiators of glutamate receptors

The present invention provides compounds having the Formula I The present invention also provides pharmaceutical compositions comprising a compound of Formula I and methods of treatment of atherosclerosis, obesity, restenosis, coronary heart disease, hyperlipoproteinemia, hypercholesterolemia, and hypertriglyceridemia.

Amide inhibitors of microsomal triglyceride transfer protein

Publisher Summary This chapter provides an update on pyridine and piperidine alkaloids. Cardiovascular effects of nicotine and cotinine have been studied. One study reported an increase in blood pressure in rats when nicotine, cotinine, or nornicotine was administered. A long term study of the effects of cotinine indicated no significant changes in blood pressure, but a decreased heart rate was observed. Nicotine inhibited prostacyclin synthetase in horse aorta microsomes, while cotinine stimulated this enzyme. Both 1 and 5 increased prostaglandin E2 synthesis, while decreasing leukotriene B4 production in polymorphonuclear leukocytes, and decreased thromboxane B2 production in platelet rich plasma. Nicotine and cotinine activated platelet activating factor hydrolase, suggesting a possible role in cardiovascular disease.

Chapter Two Pyridine and piperidine alkaloids: An update

Novel prodrugs or depot derivatives of 1,2,3,4-tetra-hydro-9-acridinamine are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer"s disease, Huntington"s chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release. Embodiments of the invention have the following general structural formula: wherein X is O or CH2; and R is alkyl of from one to twenty carbon atoms, or wherein n is zero or an integer of one to twenty.

Derivatives of 1,2,3,4-tetrahydro-9-acridinamine

Cholinergic agents: Effect of methyl substitution in a series of arecoline derivatives on binding to muscarinic acetylcholine receptors

A method is disclosed for the treatment or amelioration of the symptoms of cerebral insufficiency characterized by decreased central adrenergic and/or cholinergic function employing certain N-substituted aminopyridines.

Method of treating senile cognitive decline with N'-substituted aminopyridine adrenergic agents

4-(N-Substituted amino)-2-butynyl-1-ureas and thioureas and derivatives thereof are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as centrally acting muscarinic agents and are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release.

4-(N-substituted amino)-2-butynyl-1-ureas and thioureas and derivatives thereof as centrally acting muscarinic agents

4-(N-Substituted amino)-2-butynyl-1-carbamates and thiocarbamates and derivatives thereof are described, as well as methods for the preparation and pharmaceutical compositions of same, which are useful as centrally acting muscarinic agents and are useful as analgesic agents for the treatment of pain, as sleep aids and as agents for treating the symptoms of senile dementia, Alzheimer's disease, Huntington's chorea, tardive dyskinesia, hyperkinesia, mania, or similar conditions of cerebral insufficiency characterized by decreased cerebral acetylcholine production or release.

Jeffrey Alan Kester

Papers

Derivatives of 1,2,3,4-tetrahydro-9-acridinamine

Cholinergic agents: Effect of methyl substitution in a series of arecoline derivatives on binding to muscarinic acetylcholine receptors

Method of treating senile cognitive decline with N'-substituted aminopyridine adrenergic agents

4-(N-substituted amino)-2-butynyl-1-ureas and thioureas and derivatives thereof as centrally acting muscarinic agents

4-(n-substituted amino)-2-butynyl-1-carbamates and thiocarbamates and derivatives thereof as centrally acting muscarinic agents