Dose dependent inhibition of REM sleep in normal volunteers by biperiden, a muscarinic antagonist

Gillin, J. Christian; Sutton, Laura; Ruiz, Caroline; Golshan, Shahrokh; Hirsch, Sharon; Warmann, Christine; Shiromani, Priyattam J.

doi:10.1016/0006-3223(91)90169-m

Cited by 33 publications

(16 citation statements)

References 17 publications

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“…They showed an increase of the number of REMs and REM sleep maintenance after the administration of numerous ACh-esterase inhibitors. Also, preclinical (Velazquez-Moctezuma et al, 1991;Coleman et al, 2004) and clinical (Riemann et al, 1988;Gillin et al, 1991) studies have shown that compounds with a selective affinity for M 1 mAChRs did not affect these parameters. In contrast, the ACh-esterase inhibitor tacrin did not significantly affect REM density or duration (Riemann et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, numerous ACh-esterase inhibitors (eg physostigmine: Sitaram et al, 1976;galanthamine: Riemann et al, 1994) and selective M 1 mAChR agonists, like pilocarpine (Berkowitz et al, 1990) or RS-86 (Riemann et al, 1988), shorten REM latency. Gillin et al (1991) demonstrated that low doses of the M 1 antagonist biperiden selectively enhanced REM latency without affecting REM duration. Only higher doses of biperiden associated with reduced M 1 selectivity and increasing M 2 antagonism decreased the duration of REM sleep.…”

Section: Introductionmentioning

confidence: 97%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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

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show abstract

“…While acute administration of muscarinic agonists can shorten REM latency, increase REM activity and REM density, and reduce slow-wave sleep (Berkowitz et al 1990;Riemann and Berger 1989;Riemann et al 1988;Sitaram and Gillin 1980;Sitaram et al 1977Sitaram et al , 1978, acute administration of muscarinic cholinergic antagonists generally produce the opposite effects (Gillin et al 1991b;Hohagen et al 1994;Poland et al 1989Poland et al , 1997Sagalés et al 1969;Salin-Pascual et al 1993;Sitaram et al 1978). Based upon the pharmacologic profile of the compounds used to manipulate sleep, it appears that both M1 and M2 muscarinic receptor subtypes are involved in the regulation of REM sleep and its various elements Imeri et al 1994;Velazquez-Moctezuma et al 1989, 1991Zoltoski et al 1993).…”

Section: Discussionmentioning

confidence: 99%

Age-Related Effects of Scopolamine on REM Sleep Regulation in Normal Control Subjects Relationship to Sleep Abnormalities in Depression

Rao

Lutchmansingh

Poland

1999

Neuropsychopharmacology

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In order to assess the influence of development on the regulation of rapid eye movement (REM) sleep by cholinergic systems, the REM sleep responses toElectroencephalographic (EEG) sleep changes associated with major depressive disorder are among the most well replicated findings in adult patients (for a review, see Benca et al. 1992). Perhaps the most dramatic changes occur with respect to rapid eye movement (REM) sleep measures.Despite the evidence for continuities in mood disorders across the life span (Kovacs 1996), the manifestation of comparable REM sleep abnormalities appears to occur less frequently in early onset depression (reviewed in Rao et al. 1996). The mechanisms for this disparity are unclear. One possibility is that circadian and ultradian rhythms are more desynchronized in youngsters with depression, thus not allowing the REM sleep abnormalities, particularly the shortening of REM latency, to be easily detected (Teicher et al. 1993). Another possibility is that slow-wave sleep pressure is greater than REM sleep pressure in youngsters so that the shortening of REM sleep latency is constrained (Borbely 1982).Furthermore, it is possible that the neurotransmitter circuitry involved in REM sleep regulation is not fully mature in youngsters. Thus, shortened REM latency or increased REM activity and density in depression

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“…For instance, REM sleep is suppressed following systemic 5-HT 1A agonists (Gillin et al 1994;Seifritz et al 1996) and promoted following cholinergic agonists (Sitaram et al 1976;Berger et al 1985;Gillin et al 1991b;. Muscarinic receptor antagonists, on the other hand, partially suppress REM sleep (Gillin et al 1991a), and the depletion of central serotonin enhances REM sleep Moore et al 1998Moore et al , 2001Voderholzer et al 1998). In depression, it was found that cho-S86 E. Seifritz et al N EUROPSYCHOPHARMACOLOGY 2001 -VOL .…”

Section: Aspects Of Sleep Regulationmentioning

confidence: 99%

Contribution of Sleep Physiology to Depressive Pathophysiology

Seifritz

2001

Neuropsychopharmacology

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Dose dependent inhibition of REM sleep in normal volunteers by biperiden, a muscarinic antagonist

Cited by 33 publications

References 17 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

Age-Related Effects of Scopolamine on REM Sleep Regulation in Normal Control Subjects Relationship to Sleep Abnormalities in Depression

Contribution of Sleep Physiology to Depressive Pathophysiology

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