piperidines and 2-ethyl-8-methyl-2-8-diazaspiro(4-5)decane-1-3-dione

piperidines has been researched along with 2-ethyl-8-methyl-2-8-diazaspiro(4-5)decane-1-3-dione* in 3 studies

Trials

1 trial(s) available for piperidines and 2-ethyl-8-methyl-2-8-diazaspiro(4-5)decane-1-3-dione

ArticleYear
Differential effects of the muscarinic M1 receptor agonist RS-86 and the acetylcholine-esterase inhibitor donepezil on REM sleep regulation in healthy volunteers.
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2006, Volume: 31, Issue:6

    Broad evidence from preclinical and clinical research indicates that cholinergic neurotransmission contributes significantly to the generation of rapid eye movement (REM) sleep. However, a potential role of different acetylcholine receptor (AChR) subtypes for the regulation of three main aspects of REM sleep, (1) REM onset, (2) REM maintenance, and (3) generation of REMs, are not clear. In the present double-blind, randomized and placebo-controlled study, we investigated the differential effects of the M1 muscarinic AChR (mAChR) agonist RS-86 and the ACh-esterase inhibitor donepezil to further specify the AChR subtype function on REM sleep regulation in n = 20 healthy volunteers. We found that RS-86 selectively shortened REM latency (multivariate analysis of variance post hoc contrast p = 0.024 compared to placebo, not significant for donepezil) and that donepezil specifically enhanced the duration of REM sleep (% sleep period time, p = 0.000 compared to placebo; p = 0.003 compared to RS-86) and the number of REMs (p = 0.000 compared to placebo; p = 0.000 compared to RS-86). These results provide evidence that the onset of REM sleep is, in part, mediated by M1 mAChR activity, whereas the maintenance of REM sleep and the number of REMs are mediated by non-M1, but presumably M2 mAChR activity. These findings are of interest for the understanding of sleep regulation and of neuropsychiatric disorders, such as Alzheimer's dementia and depressive disorders, whose etiopathology may involve alterations in cholinergic neurotransmission.

    Topics: Adult; Cholinesterase Inhibitors; Donepezil; Double-Blind Method; Female; Humans; Indans; Male; Multivariate Analysis; Piperidines; Reaction Time; Receptor, Muscarinic M1; Sleep, REM; Succinimides

2006

Other Studies

2 other study(ies) available for piperidines and 2-ethyl-8-methyl-2-8-diazaspiro(4-5)decane-1-3-dione

ArticleYear
Nicotinic and muscarinic agonists and acetylcholinesterase inhibitors stimulate a common pathway to enhance GluN2B-NMDAR responses.
    Proceedings of the National Academy of Sciences of the United States of America, 2014, Aug-26, Volume: 111, Issue:34

    Nicotinic and muscarinic ACh receptor agonists and acetylcholinesterase inhibitors (AChEIs) can enhance cognitive function. However, it is unknown whether a common signaling pathway is involved in the effect. Here, we show that in vivo administration of nicotine, AChEIs, and an m1 muscarinic (m1) agonist increase glutamate receptor, ionotropic, N-methyl D-aspartate 2B (GluN2B)-containing NMDA receptor (NR2B-NMDAR) responses, a necessary component in memory formation, in hippocampal CA1 pyramidal cells, and that coadministration of the m1 antagonist pirenzepine prevents the effect of cholinergic drugs. These observations suggest that the effect of nicotine is secondary to increased release of ACh via the activation of nicotinic ACh receptors (nAChRs) and involves m1 receptor activation through ACh. In vitro activation of m1 receptors causes the selective enhancement of NR2B-NMDAR responses in CA1 pyramidal cells, and in vivo exposure to cholinergic drugs occludes the in vitro effect. Furthermore, in vivo exposure to cholinergic drugs suppresses the potentiating effect of Src on NMDAR responses in vitro. These results suggest that exposure to cholinergic drugs maximally stimulates the m1/guanine nucleotide-binding protein subunit alpha q/PKC/proline-rich tyrosine kinase 2/Src signaling pathway for the potentiation of NMDAR responses in vivo, occluding the in vitro effects of m1 activation and Src. Thus, our results indicate not only that nAChRs, ACh, and m1 receptors are on the same pathway involving Src signaling but also that NR2B-NMDARs are a point of convergence of cholinergic and glutamatergic pathways involved in learning and memory.

    Topics: Animals; CA1 Region, Hippocampal; Cholinesterase Inhibitors; Donepezil; Excitatory Postsynaptic Potentials; Indans; Long-Term Potentiation; Muscarinic Agonists; Nicotine; Nicotinic Agonists; Piperidines; Rats; Rats, Sprague-Dawley; Receptor, Muscarinic M1; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Succinimides

2014
cGMP formation and phosphoinositide turnover in rat brain slices are mediated by pharmacologically distinct muscarinic acetylcholine receptors.
    European journal of pharmacology, 1991, Jul-12, Volume: 207, Issue:3

    The cGMP response and the accumulation of inositol monophosphate (IP) induced by carbachol were compared in slices of different rat brain structures. Basal cGMP and the responses of cGMP to carbachol appeared dependent on the concentration of added Ca2+, suggesting that distinct Ca(2+)-mediated and Ca(2+)-sensitive muscarinic receptor-mediated mechanisms stimulate guanylate cyclase. Regional responses of cGMP to carbachol or to direct stimulation of guanylate cyclase with sodium nitroprusside were markedly distinct, indicating that a major proportion of guanylate cyclase in the cortex, an intermediate proportion in other forebrain regions, and only a minor proportion in the brainstem is sensitive to muscarinic receptor stimulation. The regional patterns of IP and cGMP responses to carbachol were different in the forebrain. Maximal IP accumulation was found in the cortex, whereas cGMP responses were highest in the hippocampus. Moreover, IP and cGMP formation in the hippocampus were differently antagonized by atropine, 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP), the M2-receptor subtype-preferring antagonist AF-DX 116 and the M1-selective antagonist pirenzepine. These data support the notion that the IP formation induced by carbachol in the forebrain predominantly is mediated by muscarinic receptors of the M1 subtype, and indicate the involvement of muscarinic receptors of the M3 subtype in the carbachol-induced cGMP formation.

    Topics: Animals; Atropine; Brain; Carbachol; Cyclic GMP; Guanylate Cyclase; Hippocampus; Inositol Phosphates; Male; Nitroprusside; Phosphatidylinositols; Piperidines; Rats; Rats, Inbred Strains; Receptors, Muscarinic; Succinimides

1991