The effects of an orally administered cholinergic agonist on REM sleep in major depression

Perlis, Michael L.; Smith, Michael T.; Orff, Henry J.; Andrews, Patrick J.; Gillin, J. Christian; Giles, Donna E.

doi:10.1016/s0006-3223(01)01287-2

Cited by 32 publications

(26 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The finding that numerous ACh-esterase inhibitors shorten REM latency (eg physostigmine; Sitaram et al, 1976) is consistent but does not further contribute to the discussion of the involvement of AChR subtypes. As in previous studies in younger healthy subjects (Kanbayashi et al, 2002;Perlis et al, 2002), donepezil did not significantly alter REM sleep latency in comparison to placebo. The tendency towards a reduction in REM latency by donepezil in our sample (p ¼ 0.063) may reflect a weak activation of M 1 mAChRs that may reach significance if a larger sample size were studied.…”

Section: Discussionsupporting

confidence: 81%

“…The absence of a statistically significant reduction in REM latency by donepezil, therefore, may represent a false-negative result, or a type II error. The finding that donepezil clearly shortened REM latency in depressed subjects (Perlis et al, 2002) points to a differential responsiveness to cholinergic agents based on history of depressive disorder. Interestingly, RS-86, after advancing the onset of the first REM period, also appeared to advance the occurrence of succeeding REM periods relative to sleep onset even when the duration of each REM/NREM cycle was unaffected.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Nissen

Nofzinger

Feige

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

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 M 1 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 ¼ 20 healthy volunteers. We found that RS-86 selectively shortened REM latency (multivariate analysis of variance post hoc contrast p ¼ 0.024 compared to placebo, not significant for donepezil) and that donepezil specifically enhanced the duration of REM sleep (% sleep period time, p ¼ 0.000 compared to placebo; p ¼ 0.003 compared to RS-86) and the number of REMs (p ¼ 0.000 compared to placebo; p ¼ 0.000 compared to RS-86). These results provide evidence that the onset of REM sleep is, in part, mediated by M 1 mAChR activity, whereas the maintenance of REM sleep and the number of REMs are mediated by non-M 1 , but presumably M 2 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.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 91%

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Nissen

Nofzinger

Feige

et al. 2005

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Both arecoline (Sitaram et al, 1980) and donepezil, a cholinesterase inhibitor (Perlis et al, 2002) decrease REM latency in patients with major depression, but not in healthy controls.…”

Section: Discussionmentioning

confidence: 90%

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Benson

Carson

Kiesewetter

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET). Procaine's high muscarinic affinity, together with the distribution of muscarinic receptors that overlaps with brain regions activated by procaine, suggests a muscarinic contribution to procaine's emotional and sensory effects. This study evaluates the effects of procaine on cerebral muscarinic cholinergic receptors in the anesthetized rhesus monkey. Whole brain and regional muscarinic receptor binding was measured before and after procaine administration on the same day in three anesthetized rhesus monkeys with PET and the radiotracer 3-(3-(3[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine ([ 18 F]FP-TZTP), a cholinergic ligand that has preferential binding to muscarinic (M 2 ) receptors. On separate days each animal received six different doses of i.v. procaine in a randomized fashion. Procaine blocked up to B90% of [ 18 F]FP-TZTP specific binding globally in a dose-related manner. There were no regional differences in procaine's inhibitory concentration for 50% blockade (IC 50 ) for [ 18 F]FP-TZTP. Tracer delivery, which was highly correlated to cerebral blood flow in previous monkey studies, was significantly increased at all doses of procaine with the greatest increases occurring near procaine's IC 50 for average cortex. Furthermore, anterior limbic regions showed greater increases in tracer delivery than nonlimbic regions. Procaine has high affinity to muscarinic M 2 receptors in vivo in the rhesus monkey. This, as well as a preferential increase of tracer delivery to paralimbic regions, suggests that action at these receptors could contribute to i.v. procaine's emotional and sensory effects in man. These findings are consistent with other evidence of cholinergic modulation of mood and emotion.

show abstract

“…Pilocarpine is a cholinergic agonist with a moderate affinity with M 1 muscarinic receptors and high affinity with M 5 ones. Muscarinic cholinergic agonists have effects on rapid eyes movement (REM) and slow wave sleep, playing a role in REM induction (MacGregor et al, 1997;Perlis et al, 2002). On the other hand, pilocarpine at a high dose (400 mg/kg, i.p.)…”

Section: Pathophysiology Of Seizures In Epilepsy Model Induced By Pilmentioning

confidence: 99%

“…The hippocampus is the most affected area by pilocarpine-induced seizures. Other authors also characterized the neuropathology associated with this convulsive process in striatum, frontal cortex, thalamus and amygdala (Perlis et al, 2002;Freitas et al, 2004). Seizures represent one of the most severe in vivo stimulatory stress that the brain is exposed to and generalized status epilepticus represents a very severe form of seizures.…”

Section: Pathophysiology Of Seizures In Epilepsy Model Induced By Pilmentioning

confidence: 99%

Antioxidant Treatments: Effect on Behaviour, Histopathological and Oxidative Stress in Epilepsy Model

Freitas¹

2012

Brain Injury - Pathogenesis, Monitoring, Recovery and Management

View full text Add to dashboard Cite

The effects of an orally administered cholinergic agonist on REM sleep in major depression

Cited by 32 publications

References 34 publications

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

Differential Effects of the Muscarinic M1 Receptor Agonist RS-86 and the Acetylcholine-Esterase Inhibitor Donepezil on REM Sleep Regulation in Healthy Volunteers

A Potential Cholinergic Mechanism of Procaine's Limbic Activation

Antioxidant Treatments: Effect on Behaviour, Histopathological and Oxidative Stress in Epilepsy Model

Contact Info

Product

Resources

About