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Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice.
The M2 muscarinic receptor subtype, besides its well documented involvement in the regulation of heart rate, plays a key role in mediating muscaric receptor-dependent movement and temperature control as well as antinociceptive responses, three of the most prominent central muscarinate effects.
Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease.
The observed improvements in ADAS-Cog and CIBIC+ following treatment with xanomeline provide the first evidence, from a large-scale, placebo-controlled clinical trial, that a direct-acting muscarinic receptor agonist can improve cognitive function in patients with AD.
Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice
The present findings support the hypothesis that antagonism at 5-HT2A receptors contributes to the in vivo actions of atypical antipsychotics such as olanzapine and clozapine, and indicate that PCP increases locomotor activity, at least in part, due to actions at5- HT2A, but not 5- HT3 or5-HT1A, receptors.
Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft
Data show that abemaciclib crosses the blood–brain barrier and confirm that both CDK4 and CDK6 inhibitors reach unbound brain levels in rodents that are expected to produce enzyme inhibition; however, abemACiclib brain levels are reached more efficiently at presumably lower doses than palbociclib and are potentially on target for a longer period of time.
Xanomeline: a novel muscarinic receptor agonist with functional selectivity for M1 receptors.
The present data are consistent with the interpretation that xanomeline is a novel muscarinic receptor agonist with functional selectivity for M1 mus carinic receptors both in vitro and in vivo.
Muscarinic cholinergic modulation of prepulse inhibition of the acoustic startle reflex.
  • C. K. Jones, H. Shannon
  • Chemistry, Medicine
    The Journal of pharmacology and experimental…
  • 1 September 2000
The present findings demonstrate that the muscarinic cholinergic system plays an important role in the normal mechanisms of PPI, and is reversed in a dose-dependent manner by the mus carinic receptor agonist oxotremorine.
Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice
The activation of bothmGlu2 and mGlu3 receptors by LY354740 appears to be required for anxiolytic-like activity in the EPM test in mice, and these studies serve as a foundation for additional studies on underlying circuits, brain structures, and receptor subtypes involved in the anxiety-related actions of mGLU receptor active agents, and the design of future drugs for anxiety disorders in humans.
Pharmacologic Interactions between the Muscarinic Cholinergic and Dopaminergic Systems in the Modulation of Prepulse Inhibition in Rats
It is demonstrated that a functional interaction occurs between the mus carinic cholinergic and dopaminergic systems in modulating PPI and that muscarinic Cholinergic receptor agonists may be effective in the treatment of the P PI and other cognitive impairments observed in schizophrenia.
Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice.
  • J. Gomeza, L. Zhang, +7 authors J. Wess
  • Biology, Medicine
    Proceedings of the National Academy of Sciences…
  • 31 August 1999
Results indicate that M(4) receptors exert inhibitory control on D1 receptor-mediated locomotor stimulation, probably at the level of striatal projection neurons where the two receptors are coexpressed at high levels.
Comparison of the effect of glutamate receptor modulators in the 6 Hz and maximal electroshock seizure models
The results from the present study support the continued search for glutamate receptor modulators as potential antiepileptic agents and illustrate the importance of using several different animal seizure models in the search for novel AEDs.