Influence of Biperiden and Bornaprine on Sleep in Healthy Subjects

Abstract

mg, an anticholinergic drug that is relatively selective for the Ml receptor subtype, and bornaprine, 4 mg, a nonselective Ml and M2 antagonist, were administered orally in a randomized, double-blind design to twelve healthy volunteers to investigate the effect on polysomnographically recorded sleep. Both drugs suppressed rapid eye movement (REM) sleep as reflected by an increase of REM latency and a decrease in the KEY WORDS: Bornaprine; Biperiden; Cholinergic system; REM sleep; Slow wave sleep There is strong evidence that the cholinergic system is involved in the generation of rapid eye movement (REM) sleep (Hobson et al. 1986). Whereas the trigger ing of REM sleep by cholinergic neurons has been demonstrated convincingly (Hobson et al. 1975(Hobson et al. , 1986Shiromani et al. 1987), it is still a question as to the ex tent muscarinic M1 and/or M2 receptors are involved in REM sleep regulation. Results of a recent study based on the microinjection of cholinomimetic drugs at the medial pontine-reticular formation in cats suggest that physiological and cholinergically induced REM sleep is mediated primarily by the M2 subtype of muscarinic receptors (Velazquez-Moctezuma et al. 1989, 1990. In comparison, biperiden, a preferential M1 antagonist, increased REM sleep latency, and reduced REM sleep time in healthy volunteers (Gillin et al. 1991;Salin Pascual et al. 1991.The aim of the present study was to investigate the effect of biperiden and bomaprine, two cholinergic an tagonists, on sleep, especially REM sleep, in healthy subjects. The pharmacokinetic properties of both drugs are similar (Hollmann et al. 1984;Grimaldi et al. 1986;Mayo et al. 1980). Biperiden is considered to be a highly selective M1 antagonist (Burke 1986; Syvalahti et al. 1988;Eltze and Figala 1988;Freedman et al. , 1988) with a M1 selectivity similar to that of pirenzepine (Syvalahti et al. 1987;Avissar and Schreiber 1989;Larson et al. 1991). Bomaprine, another centrally acting anticholiner gic drug, lacks selectivity for the M1 or M2 receptor hav ing equal affi nity to both receptor subtypes (Kreiskott and Kretschmar 1985). The antagonism of bomaprine at the M2 muscarinic receptor has been demonstrated (Huff ord et al., 1991). If M2 receptors are mainly respon sible for the generation of REM sleep, a nonselective anticholinergic drug like bomaprine, that also shows M2 antagonistic properties, should have stronger REM sleep-suppressing effects compared to a preferential M1 receptor antagonist like biperiden. SUBJECTS AND METHODSWe investigated 12 healthy volunteers with a mean age (±SD) of 25.01 ± 1.9 years (range 22-28 years) who

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

“…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).…”