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A preliminary study of the effects of m-CPP on sleep architecture and behavior in healthy volunteers
52A
BIOLPSYCHIATR> 1989;25:42A-53A
Studies in basic and Uinical I%ychophannacolog>
106 ORAL D-FENFLURAMINE AS A SEROTONINERGIC CHALLENGE TEST IN HUMAN SUBJECTS Trevor Silverstone, Sean Feeney London, England
Fenfluramine, the racemic mixture of d- and I-fenfluramine elevates prolactin (PRL) levels in normal subjects, possibly via a serotoninergic (5-HT) mechanism. In animals the d-isomer (d-FF) has been shown to be highly selective for 5-HT neurotransmitter pathways, enhancing release and blocking reuptake. The present investigation was undertaken to measure the effect of oral d-FF on PRL levels with a view to examining its potential as a serotoninergic challenge test. Twelve healthy male subjects reported after an overnight fast. On one occasion they received a single oral dose of 30 mg dFF, on another matching placebo. The order was random, and there was at least one week interval between the two occasions. The study was conducted according to a double-blind crossover design. Blood was taken from an indwelling catheter before medication and at two hourly intervals thereafter over a six hour period. After centrifugation and separation of plasma the level of PRL was determined using a radioimmunoassay procedure. d-FF caused a significantly greater rise in plasma PRL than placebo. Thus the PRL response to a single oral dose of 30 mg d-FF would appear to provide a simple and reliable 5-HT challenge test for use in human subjects.
107 A PRELIMINARY STUDY OF THE EFFECTS OF M-CPP ON SLEEP ARCHITECTURE AND BEHAVIOR IN HEALTHY VOLUNTEERS B.A. Lawlor, P.A. Newhouse, T. Balkin, S.E. Molchan, A.M. Mellow, D.L. Murphy, T. Sunderland Bethesda, MD
Meta-chlorophenylpiperazine (m-CPP), a metabolite of the antidepresant trazodone, has relative selectivity for the serotonin (5HT) system and may affect the serotonergic mechanisms of sleep. In a pilot study, we examined the effects of m-CPP (0.5 mg/ kg po) on sleep architecture and behavior in six healthy volunteers (mean age 41.5 -+: 22.4). Subjects first underwent a single habituation night followed by two study nights (separated by at least 72 hours). m-CPP was administered in a doubleblind placebo-controlled randomized fashion. Sleep EEG electrodes were applied according to standard practice and attached to an ambulatory EEG recorder. EEG recordings were scored blind to treatment conditions. m-CPP significantly reduced total sleep time without affecting the percentage of time spent in different sleep stages, particularly slow wave sleep. Five out of six subjects reported prominent behavioral effects (racing thoughts, restlessness, and mild perceptual distortions) that interfered with sleep onset. The finding of a marked reduction in total sleep time is in contrast to self-reports of increased sleepiness following daytime administration of m-CPP in some human studies. The behavioral activating effects of m-CPP and the small number of subjects in this study may explain the lack of a specific effect of m-CPP on slow wave sleep. The marked behavioral effects following nighttime administration of mCPP suggest that the context of the experiment or circadian variation in 5-HT function could influence the responsivity of the system to 5-HT stimulation.
BIOLPSYCHIATR> 1989;25:42A-53A
Studies in basic and Uinical I%ychophannacolog>
106 ORAL D-FENFLURAMINE AS A SEROTONINERGIC CHALLENGE TEST IN HUMAN SUBJECTS Trevor Silverstone, Sean Feeney London, England
Fenfluramine, the racemic mixture of d- and I-fenfluramine elevates prolactin (PRL) levels in normal subjects, possibly via a serotoninergic (5-HT) mechanism. In animals the d-isomer (d-FF) has been shown to be highly selective for 5-HT neurotransmitter pathways, enhancing release and blocking reuptake. The present investigation was undertaken to measure the effect of oral d-FF on PRL levels with a view to examining its potential as a serotoninergic challenge test. Twelve healthy male subjects reported after an overnight fast. On one occasion they received a single oral dose of 30 mg dFF, on another matching placebo. The order was random, and there was at least one week interval between the two occasions. The study was conducted according to a double-blind crossover design. Blood was taken from an indwelling catheter before medication and at two hourly intervals thereafter over a six hour period. After centrifugation and separation of plasma the level of PRL was determined using a radioimmunoassay procedure. d-FF caused a significantly greater rise in plasma PRL than placebo. Thus the PRL response to a single oral dose of 30 mg d-FF would appear to provide a simple and reliable 5-HT challenge test for use in human subjects.
107 A PRELIMINARY STUDY OF THE EFFECTS OF M-CPP ON SLEEP ARCHITECTURE AND BEHAVIOR IN HEALTHY VOLUNTEERS B.A. Lawlor, P.A. Newhouse, T. Balkin, S.E. Molchan, A.M. Mellow, D.L. Murphy, T. Sunderland Bethesda, MD
Meta-chlorophenylpiperazine (m-CPP), a metabolite of the antidepresant trazodone, has relative selectivity for the serotonin (5HT) system and may affect the serotonergic mechanisms of sleep. In a pilot study, we examined the effects of m-CPP (0.5 mg/ kg po) on sleep architecture and behavior in six healthy volunteers (mean age 41.5 -+: 22.4). Subjects first underwent a single habituation night followed by two study nights (separated by at least 72 hours). m-CPP was administered in a doubleblind placebo-controlled randomized fashion. Sleep EEG electrodes were applied according to standard practice and attached to an ambulatory EEG recorder. EEG recordings were scored blind to treatment conditions. m-CPP significantly reduced total sleep time without affecting the percentage of time spent in different sleep stages, particularly slow wave sleep. Five out of six subjects reported prominent behavioral effects (racing thoughts, restlessness, and mild perceptual distortions) that interfered with sleep onset. The finding of a marked reduction in total sleep time is in contrast to self-reports of increased sleepiness following daytime administration of m-CPP in some human studies. The behavioral activating effects of m-CPP and the small number of subjects in this study may explain the lack of a specific effect of m-CPP on slow wave sleep. The marked behavioral effects following nighttime administration of mCPP suggest that the context of the experiment or circadian variation in 5-HT function could influence the responsivity of the system to 5-HT stimulation.