Cholinergic abnormalities in Alzheimer's disease: are there new targets for drug development?

Fodero, Lisa R.; Small, David H.

doi:10.1002/ddr.10089

Cited by 3 publications

(1 citation statement)

References 159 publications

(119 reference statements)

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“…SR 141716), like the reversible cholinesterase inhibitors (e.g. donepezil; for review, see Fodero & Small, 2002), increase synaptic acetylcholine levels might mean that CB 1 receptor inverse agonists/antagonists might represent a new class of cognition‐enhancing agents for use in humans. In this context, it is of interest that CB 1 receptor‐mediated inhibition of acetylcholine release and its facilitation by SR 141716 have recently also been shown in superfused slices of the human brain (Steffens et al ., 2002).…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid CB₁ receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Redmer

Kathmann

Schlicker

2003

British J Pharmacology

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1 The cannabinoid CB 1 receptor inverse agonist/antagonist SR 141716 increases acetylcholine release in rodent hippocampus and improves memory in some experimental paradigms. Since drugs like SR 141716 may represent a novel class of cognition-enhancing drugs, we wanted to check whether the function of the CB 1 receptor is preserved during ageing. 2 Hippocampal and striatal slices from 2-to 3-and 24-to 28-month-old C57BL/6J mice were preincubated with [ 3 H]-choline or [ 3 H]-noradrenaline ([ 3 H]-NA) and superfused. 3 The cannabinoid receptor agonist WIN 55,212-2 inhibited, and SR 141716 facilitated, the electrically (3 Hz) evoked tritium overflow in hippocampal slices (preincubated with [ 3 H]-choline) from young and aged mice to the same extent. The evoked overflow per se was less by 33% in slices from aged animals. 4 WIN 55,212-2 and SR 141716 did not affect, but the muscarinic receptor agonist oxotremorine inhibited, the evoked (3 Hz) overflow in striatal slices (preincubated with [ 3 H]-choline) from young and aged mice to the same extent. The evoked overflow per se tended to be less in slices from aged animals. 5 The evoked (0.3 Hz) overflow in hippocampal slices (preincubated with [ 3 H]-NA) was not affected by WIN 55,212-2 and SR 141716, but was inhibited by histamine (via H 3 receptors) in slices from young mice and, to a somewhat less extent, in slices from aged mice. The evoked overflow per se did not differ between age groups. 6 In conclusion, the function of the CB 1 receptor involved in the tonic inhibition of hippocampal acetylcholine release is preserved in aged mice.

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Section: Introductionmentioning

confidence: 99%

Cannabinoid CB₁ receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Redmer

Kathmann

Schlicker

2003

British J Pharmacology

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Current Awareness in Geriatric Psychiatry

2003

Int J Geriat Psychiatry

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of geriatric psychiatry. Each bibliography is divided into 9 sections: 1 Books, Reviews & Symposia; 2 General; 3 Assessment; 4 Epidemiology; 5 Therapy; 6 Care; 7 Dementia; 8 Depression; 9 Psychology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted

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Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application

Millan

2006

Pharmacology & Therapeutics

481

503

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Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset of action, and all provoke distressing side effects. Cloning of the human genome has fuelled expectations that symptomatic treatment may soon become more rapid and effective, and that depressive states may ultimately be "prevented" or "cured". In pursuing these objectives, in particular for genome-derived, non-monoaminergic targets, "specificity" of drug actions is often emphasized. That is, priority is afforded to agents that interact exclusively with a single site hypothesized as critically involved in the pathogenesis and/or control of depression. Certain highly selective drugs may prove effective, and they remain indispensable in the experimental (and clinical) evaluation of the significance of novel mechanisms. However, by analogy to other multifactorial disorders, "multi-target" agents may be better adapted to the improved treatment of depressive states. Support for this contention is garnered from a broad palette of observations, ranging from mechanisms of action of adjunctive drug combinations and electroconvulsive therapy to "network theory" analysis of the etiology and management of depressive states. The review also outlines opportunities to be exploited, and challenges to be addressed, in the discovery and characterization of drugs recognizing multiple targets. Finally, a diversity of multi-target strategies is proposed for the more efficacious and rapid control of core and co-morbid symptoms of depression, together with improved tolerance relative to currently available agents.

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Cholinergic abnormalities in Alzheimer's disease: are there new targets for drug development?

Cited by 3 publications

References 159 publications

Cannabinoid CB₁ receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Cannabinoid CB₁ receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Current Awareness in Geriatric Psychiatry

Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application

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Cholinergic abnormalities in Alzheimer's disease: are there new targets for drug development?

Cited by 3 publications

References 159 publications

Cannabinoid CB1 receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Cannabinoid CB1 receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Current Awareness in Geriatric Psychiatry

Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application

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Product

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Cannabinoid CB₁ receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice

Cannabinoid CB₁ receptor‐mediated inhibition of hippocampal acetylcholine release is preserved in aged mice