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1.
J Clin Psychopharmacol ; 30(1): 18-24, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20075643

RESUMEN

OBJECTIVES: To compare the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) with placebo in reducing relapse rate in patients with major depressive disorder (MDD). METHODS: This phase 3, multicenter, randomized trial included a 12-week, open-label (OL) treatment phase (intent-to-treat population, n = 575) followed by a 6-month, double-blind (DB) relapse prevention phase. Patients who responded to the OL treatment (17-item Hamilton Rating Scale for Depression total score or= 16 at any visit, Clinical Global Impression-Improvement score >or= 6 at any visit, or discontinuation due to unsatisfactory response). RESULTS: Patients receiving desvenlafaxine (n = 189) experienced significantly longer times to relapse of MDD versus patients receiving placebo (n = 185) during the DB period (log-rank test, P < 0.0001). The percentages of patients relapsing were 42% (78/185) and 24% (45/189) for placebo and desvenlafaxine, respectively (P < 0.001). The most common primary reason cited for discontinuation in the OL period was adverse events (19%), which consisted of nausea, dizziness, and insomnia. A total of 159 patients (42%) discontinued treatment during the DB period, including 101 placebo- (55%) and 58 desvenlafaxine-treated patients (31%). The most frequent adverse event reported as reason for treatment discontinuation in the DB period was depression, reported by 14 placebo- (8%) and 7 desvenlafaxine-treated patients (4%). CONCLUSIONS: Desvenlafaxine effectively prevented relapse of MDD during 6 months of DB treatment in patients who had responded to 12 weeks of OL desvenlafaxine therapy.


Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adulto , Antidepresivos/efectos adversos , Ciclohexanoles/efectos adversos , Trastorno Depresivo Mayor/prevención & control , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Prevención Secundaria , Resultado del Tratamiento
2.
J Child Neurol ; 34(5): 248-255, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30688135

RESUMEN

Efficacy and safety of pregabalin as adjunctive treatment for children (aged 4-16 years) with partial-onset seizures, hereafter termed focal onset seizures for this study, was evaluated. This double-blind, randomized, placebo-controlled, international study had 3 phases: 8-week baseline, 12-week double-blind treatment (2-week dose escalation; 10-week fixed dose), and 1-week taper. Selection criteria included experiencing focal onset seizures and receiving a stable regimen of 1 to 3 antiepileptic drugs. Study treatments were pregabalin 2.5 mg/kg/d, 10 mg/kg/d, or placebo; doses were increased to 3.5 or 14 mg/kg/d for subjects weighing <30 kg. The key endpoints were change in loge(28-day seizure rate), achieving a ≥50% seizure responder rate, safety, and tolerability during double-blind treatment. Subjects (n = 295; mean age 10.2 years, 55% male, 69% white) were randomized to pregabalin 2.5 mg/kg/d (n = 104), 10 mg/kg/d (n = 97), or placebo (n = 94). A statistically significant reduction in loge(28-day seizure rate) was demonstrated with pregabalin 10 mg/kg/d (a 19.9% improvement over placebo; P = .0185). Seizure frequency was numerically improved (statistically nonsignificant) with pregabalin 2.5 mg/kg/d ( P = .2577). Responder rate significantly favored pregabalin 10 mg/kg/d (40.6%, P = .0068) compared with placebo (22.6%) and was numerically improved with pregabalin 2.5 mg/kg/d (29.1%, P = .2600). Common adverse events (≥10% of any group) in 10 mg/kg/d, 2.5 mg/kg/d, and placebo groups, respectively, included somnolence (25.8%, 17.3%, 13.8%), increased weight (13.4%, 3.8%, 4.3%), and increased appetite (10.3%, 6.7%, 4.3%). Pregabalin 10 mg/kg/d demonstrated efficacy in seizure frequency reduction in children with focal onset seizures compared with placebo, and both pregabalin doses were generally safe and well tolerated. www.clinicialtrials.gov identifier NCT01389596; EudraCT #2010-020852-79.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Pregabalina/uso terapéutico , Convulsiones/tratamiento farmacológico , Adolescente , Anticonvulsivantes/efectos adversos , Niño , Preescolar , Método Doble Ciego , Quimioterapia Combinada , Epilepsias Parciales/tratamiento farmacológico , Femenino , Humanos , Masculino , Pregabalina/efectos adversos , Resultado del Tratamiento
3.
Int Clin Psychopharmacol ; 23(4): 188-97, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18545056

RESUMEN

The efficacy, safety, and tolerability of desvenlafaxine (administered as desvenlafaxine succinate) were evaluated in two similarly designed, phase 3, randomized, double-blind, placebo-controlled, venlafaxine-extended-release-referenced, flexible-dose studies of outpatients with a primary diagnosis of major depressive disorder. Owing to a high placebo response, the individual studies were underpowered. Therefore, a post-hoc pooled analysis was performed (desvenlafaxine and placebo data were pooled; venlafaxine extended release data were not, owing to different flexible-dose regimens in the two studies). The primary outcome measure was the change from baseline on the 17-item Hamilton Rating Scale for Depression; the Clinical Global Impressions-Improvement item score was a secondary outcome. Analysis of the pooled data (using a mixed-effect model for repeated measures) revealed that after 8 weeks of treatment, desvenlafaxine was significantly better than placebo on 17-item Hamilton Rating Scale for Depression [-14.21 vs. -11.87 for desvenlafaxine and placebo, respectively; magnitude of effect=-2.34 (P<0.001)] and Clinical Global Impressions-Improvement item scores [1.95 vs. 2.32 for desvenlafaxine and placebo, respectively; magnitude of effect=-0.37 (P<0.001)]. Adverse events were comparable to those found with other drugs sharing a similar mechanism of action. These data support the efficacy, safety, and tolerability of desvenlafaxine in the treatment of major depressive disorder.


Asunto(s)
Inhibidores de Captación Adrenérgica/uso terapéutico , Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores de Captación Adrenérgica/efectos adversos , Antidepresivos/efectos adversos , Ciclohexanoles/efectos adversos , Succinato de Desvenlafaxina , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos
4.
Int Clin Psychopharmacol ; 22(6): 338-47, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17917552

RESUMEN

The antidepressant efficacy and safety of desvenlafaxine succinate (desvenlafaxine) were evaluated in a phase III, double-blind, placebo-controlled study. Outpatients with a primary diagnosis of major depressive disorder were treated with fixed once-daily doses of desvenlafaxine 200 or 400 mg for 8 weeks. The primary efficacy measure was change from baseline on the 17-item Hamilton Rating Scale for Depression. At the final on-therapy evaluation, adjusted mean change from baseline in 17-item Hamilton Rating Scale for Depression total score was greater for desvenlafaxine 200 and 400 mg/day vs. placebo. Both desvenlafaxine doses showed greater efficacy than placebo on the secondary efficacy measures, including the Clinical Global Impressions-Improvement scale scores, Montgomery-Asberg Depression Rating Scale scores, CGI-Severity, and 17-item Hamilton Rating Scale for Depression response rate. Desvenlafaxine 200 mg/day was also significantly better than placebo on remission, Visual Analog Scale-Pain Intensity overall scores, and some Visual Analog Scale-Pain Intensity subscale scores. Desvenlafaxine 400 mg/day was significantly better than placebo on selected Visual Analog Scale-Pain Intensity subscale scores. Most adverse events were mild or moderate in severity, and safety assessments revealed few clinically significant changes in vital signs, laboratory tests, and electrocardiogram results. These data provide support for the efficacy and safety of desvenlafaxine in the treatment of major depressive disorder.


Asunto(s)
Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Ciclohexanoles/efectos adversos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Mareo/inducido químicamente , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Escalas de Valoración Psiquiátrica , Factores Sexuales , Sudoración/efectos de los fármacos , Resultado del Tratamiento
5.
J Biol Rhythms ; 17(1): 52-64, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11837949

RESUMEN

Little information is available on circadian organization in diurnal mammals. In the present study, the daily patterns of wheel-running activity were described in a diurnal rodent, Arvicanthis ansorgei Thomas 1910, as assessed by karyological analysis. Among 108 animals born in the colony and studied under a 12:12 light-dark cycle (lights on at 7:00 a.m.), the authors determined the timing of daily activity (i.e., mean onsets and offsets of pattern of locomotor activity) and the level of wheel-running activity performed during daytime versus nighttime. The activity pattern was essentially diurnal in 84% of individuals, 46% being active only during the light period +/- 1 h (activity onsets and offsets at 6:20 a.m. and 7:40 p.m., respectively) and 38% being diurnal with a period of nocturnal activity longer than 1 h (activity onsets and offsets at 5:40 a.m. and 9:30 p.m., respectively). Of the 108 animals, 16% expressed a nocturnal activity with diurnal overlaps no longer than 1 h. In 6 diurnal individuals first exposed to constant light and then to constant dim red light, the endogenous period was shortened from 24.6 +/- 0.1 to 24.0 +/- 0.1 h, respectively. The numbers of wheel revolutions per day and during the active period remained unchanged between the two lighting conditions. In response to different photoperiodic changes from 16:08 to 08:16 light-dark cycles, the phase angle of photic synchronization, estimated by the daily onset of wheel-running activity in 6 diurnal animals, showed marked changes, its timing occurring 2 h before and 0.5 h after the onset of light under short and long photoperiods, respectively. The numbers of wheel revolutions per 24 h and during the active period were modified similarly according to photoperiodic changes. Finally, in 5 diurnal animals exposed to a 12:12 light-dark cycle, the daily pattern of general locomotor activity, determined by telemetry, was not modified by wheel availability. The data indicate that A. ansorgei is an interesting experimental model to understand the regulation of the circadian timing system in day-active species.


Asunto(s)
Ritmo Circadiano/fisiología , Muridae/fisiología , Fotoperiodo , Animales , Ritmo Circadiano/genética , Femenino , Cariotipificación , Luz , Masculino , Actividad Motora/fisiología , Muridae/genética , Telemetría
6.
J Clin Psychiatry ; 65(6): 838-44, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15291662

RESUMEN

BACKGROUND: This retrospective analysis evaluated the prevalence and severity of pre-treatment gastrointestinal (GI) symptoms in patients with generalized anxiety disorder (GAD), the impact of these GI symptoms on the efficacy and tolerability of venlafaxine extended-release (XR), and the effect of treatment on prestudy GI symptoms. METHOD: Data from 1932 nondepressed GAD patients were pooled from 5 randomized, double-blind, placebo-controlled studies of venlafaxine XR clinically conducted between May 1995 and December 1997. The GI symptom severity at baseline was estimated from item 11 on the Hamilton Rating Scale for Anxiety (HAM-A). Patients with a GI symptom severity score < or = 2 (moderate or less) and those with a GI symptom severity score > 2 (severe/very severe) were compared for baseline characteristics and short-term (8-week) and long-term (24-week) outcomes. RESULTS: At baseline, for all randomized patients with a HAM-A item 11 score, GI symptoms were rated moderate or lower in 82.8% of patients (GI-low) and severe/very severe in 17.2% (GI-high). The GI-high subgroup was statistically significantly (p < .05) younger, had a longer duration of GAD, and had higher mean HAM-A total scores than the GI-low subgroup. Compared with placebo, venlafaxine XR significantly reduced HAM-A total and psychic anxiety factor scores, regardless of baseline GI symptom severity. The incidence of adverse events, particularly nausea, was higher for the GI-high versus GI-low subgroup. CONCLUSION: Baseline severity of GI symptoms correlated with overall severity of GAD but had no impact on treatment outcome with venlafaxine XR. These data do not support the hypothesis that high baseline GI symptom severity has a negative effect on treatment with venlafaxine XR in GAD patients.


Asunto(s)
Trastornos de Ansiedad/tratamiento farmacológico , Ciclohexanoles/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Adulto , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Ciclohexanoles/uso terapéutico , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/epidemiología , Humanos , Masculino , Pacientes Desistentes del Tratamiento , Placebos , Escalas de Valoración Psiquiátrica , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Clorhidrato de Venlafaxina
7.
Behav Brain Res ; 133(2): 343-50, 2002 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-12110468

RESUMEN

Melatonin entrains circadian rhythms in several species of rodents, but a role for melatonin as a Zeitgeber in the adult Syrian hamster is debated. The aim of this study was to define the conditions of daily programmed melatonin infusion in which an entrainment of the locomotor activity rhythm is obtained in adult male Syrian hamsters. The animals were pinealectomized, cannulated with a subcutaneous infusion system and submitted to dim red light conditions. They were initially daily infused with vehicle until free-running was established. Then, the animals were divided into three experimental groups, each group corresponding to a specific melatonin dose and infusion duration: (1) 10 microg melatonin/h for 5 h; (2) 30 microg melatonin/h for 5 h; and (3) 50 microg melatonin/h for 1 h. Of the total 64 hamsters, 37 hamsters fully entrained to the melatonin infusion regardless of whether the animals expressed during pre-treatment a free-running period (tau)< or >24 h, 20 animals presented a transient entrainment and seven did not entrain. Of the 37 animals entrained, withdrawal of melatonin re-established free-running rhythms, although often with a different tau compared with that observed during pre-treatment. These results indicate that after a long time of daily infusion, melatonin is able to entrain the free-running rhythm in adult Syrian hamster. The mechanism involved is not known, but the change in tau observed after melatonin treatment in some animals suggests that melatonin, directly or indirectly, affects the functioning of the clock.


Asunto(s)
Ritmo Circadiano/efectos de los fármacos , Melatonina/farmacología , Actividad Motora/fisiología , Glándula Pineal/fisiología , Animales , Cricetinae , Inyecciones Subcutáneas , Masculino , Melatonina/administración & dosificación , Melatonina/sangre , Mesocricetus
8.
Artículo en Inglés | MEDLINE | ID: mdl-21977353

RESUMEN

BACKGROUND: The primary objective was to evaluate the long-term safety of desvenlafaxine (administered as desvenlafaxine succinate) during open-label treatment in adult outpatients with a primary DSM-IV diagnosis of major depressive disorder (MDD). METHOD: Depressed adult outpatients (≥ 18 years) who had completed 8-week, double-blind therapy (desvenlafaxine, venlafaxine extended release, or placebo) in a phase 3 study of desvenlafaxine for MDD received up to 10 months of open-label treatment with flexible-dose desvenlafaxine (200 to 400 mg/d). Safety assessments included physical examination, measurement of weight and vital signs, laboratory determinations, and 12-lead electrocardiogram recordings. Adverse events (AEs) and discontinuations due to AEs were monitored throughout the trial. The primary efficacy outcome was mean change from baseline on 17-item Hamilton Depression Rating Scale (HDRS-17) total score. The trial was conducted from August 2003 to March 2006. RESULTS: The safety population included 1,395 patients who took at least 1 dose of open-label desvenlafaxine. Treatment-emergent AEs were reported by 1,238 of 1,395 patients (89%) during the open-label, on-therapy period. Treatment-emergent AEs reported by 10% or more patients were headache, nausea, hyperhidrosis, dizziness, dry mouth, insomnia, upper respiratory infection, nasopharyngitis, and fatigue. Adverse events were the primary reason for study discontinuation in 296 of 1,395 patients (21%). Ten patients (< 1%) had serious AEs that were considered possibly, probably, or definitely related to the study drug during the on-therapy period. No deaths occurred during the study. CONCLUSIONS: Desvenlafaxine can be safely administered for up to 12 months. No new safety findings were observed in this study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01309542.

9.
Curr Med Res Opin ; 26(1): 139-50, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19919295

RESUMEN

BACKGROUND: Major depressive disorder (MDD) is a common, seriously impairing illness. Desvenlafaxine (administered as desvenlafaxine succinate) is the third serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States for the treatment of MDD. Short-term clinical studies have demonstrated the efficacy and safety of 50 to 400 mg/d doses, with no evidence that doses greater than 50 mg/d confer additional benefit. OBJECTIVE: This paper summarizes published data on the efficacy, safety, and tolerability of the desvenlafaxine 50-mg/d recommended therapeutic dose for MDD and discusses clinical practice considerations. METHODS: A systematic review of MEDLINE, PsycINFO, and PubMed (all years through June 2009) was performed using the terms desvenlafaxine, DVS, and ODV. The criteria for inclusion in the review were a double-blind design, a placebo control or active comparator group, the 50-mg desvenlafaxine dose group, and enrollment of patients with a diagnosis of MDD. Posters were included if they reported on a study that was subsequently published in a manuscript. RESULTS: Overall results of two randomized, placebo-controlled, 8-week clinical trials demonstrated the efficacy of desvenlafaxine 50 mg/d for MDD. Statistically significant improvements compared with placebo were observed on the primary efficacy measure (17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score; P < 0.05). Significant differences were observed on several secondary measures (Montgomery Asberg Depression Rating Scale scores in both trials [P < 0.05]; Clinical Global Impressions-Improvement scores [P < or = 0.01], Clinical Global Impressions-Severity scores [P < or = 0.01], HAM-D(17) response [P < or = 0.01] and remission [P < 0.05] in one trial each). Functional outcomes measures (Sheehan Disability Scale total and World Health Organization 5-Item Well-Being Index scores) were significant in both trials (P < 0.05). Safety results indicate desvenlafaxine treatment was safe and well tolerated; findings were consistent with the SNRI class. The generalizability of these findings is limited by the study protocols, which excluded patients with unstable comorbid medical conditions and also those with other Axis 1 and 2 psychiatric illnesses. Additionally, comparisons with other SNRIs are challenging given differences in study design. Desvenlafaxine can be initiated with the 50-mg/d therapeutic dose without titration and provides efficacy with rates of discontinuation due to treatment-emergent adverse events similar to placebo. In vitro data indicate desvenlafaxine has minimal inhibitory effects on cytochrome P450 (CYP) 2D6 and clinical studies show desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism. In vitro data also indicate desvenlafaxine is not a substrate or inhibitor of the p-glycoprotein transporter. Plasma protein binding of desvenlafaxine is low (30%) and independent of drug concentration. Bioavailability is high at 80% after oral administration and is not affected by food. CONCLUSIONS: Desvenlafaxine 50 mg/d has demonstrated efficacy, safety, and tolerability for the treatment of MDD in two placebo-controlled trials. The metabolic profile of desvenlafaxine suggests a low risk of drug-drug interactions owing to minimal inhibitory effects on CYP2D6, lack of interaction with p-glycoprotein, and low protein binding.


Asunto(s)
Antidepresivos/uso terapéutico , Ciclohexanoles/uso terapéutico , Trastorno Depresivo Mayor/tratamiento farmacológico , Inhibidores de la Captación de Neurotransmisores/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Antidepresivos/farmacocinética , Ciclohexanoles/administración & dosificación , Ciclohexanoles/efectos adversos , Ciclohexanoles/farmacocinética , Trastorno Depresivo Mayor/psicología , Succinato de Desvenlafaxina , Método Doble Ciego , Humanos , Inhibidores de la Captación de Neurotransmisores/administración & dosificación , Inhibidores de la Captación de Neurotransmisores/efectos adversos , Inhibidores de la Captación de Neurotransmisores/farmacocinética , Placebos , Resultado del Tratamiento
10.
J Pineal Res ; 38(3): 189-97, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15725341

RESUMEN

Like nocturnal rodents, the diurnal tropical rodent Arvicanthis ansorgei shows a daily rhythm in pineal melatonin content. Seasonal and photoperiodic variations in the biosynthetic activity of the pineal gland: arylalkylamine-N-acetyltransferase (AA-NAT), hydroxyindole-O-methyltransferase (HIOMT) activities and melatonin content were measured in male and female A. ansorgei captured near Samaya, Mali, and kept either under artificial laboratory photoperiods [light-dark (LD) cycles: LD 14:10, LD 12:12 or LD 10:14 or caught in the field in Mali and killed at four different times of the year (January, April, June and November). Under artificial photoperiod, the duration of the nocturnal peak of AA-NAT activity and melatonin content increased with the duration of the dark period while the amplitude did not significantly change. In the field, annual variations in the amplitude of the nocturnal melatonin peak were observed with a maximum in April (highest temperature, low humidity and no grass availability, only seeds) and a minimum in November (high humidity, maximum green grass availability). The variations in the amplitude of the melatonin peak were not correlated with changes in AA-NAT HIOMT activities, suggesting that seasonal variations in the amplitude of the melatonin peak are not driven by these enzymes. Daytime injections of the beta-adrenergic agonist, isoproterenol, stimulated melatonin synthesis in January, April and June, but not in November. The annual differences in the amplitude of the melatonin peak as well as the seasonal differences in the response to an adrenergic stimulation suggest that environmental factors other than photoperiod, such as temperature, humidity and consequent food availability, could be important in the regulation of the annual variations in the pineal biosynthetic activity in this species.


Asunto(s)
Adrenérgicos/farmacología , Muridae/metabolismo , Glándula Pineal/efectos de los fármacos , Glándula Pineal/metabolismo , Acetilserotonina O-Metiltransferasa/metabolismo , Agonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , N-Acetiltransferasa de Arilalquilamina/metabolismo , Ritmo Circadiano , Ambiente , Femenino , Isoproterenol/farmacología , Cinética , Masculino , Melatonina/biosíntesis , Fotoperiodo , Propranolol/farmacología , Estaciones del Año
11.
Neurosignals ; 11(2): 73-80, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12077480

RESUMEN

Entrainment of running wheel activity in DD was studied in adult male Long Evans rats exposed to cycles of a constant dose of melatonin (MEL; 100 microg/h) infused subcutaneously. The period (T) of the MEL cycle was initially kept at 24 h until stable entrainment was established; T was then changed in a stepwise manner, and each new T value was maintained for at least 20 cycles. Entrainment by phase advance occurred near circadian time 12 (activity onset), and the range of entrainment was between 30 and 35 min. The negative phase angle difference between activity onset and MEL onset increased as T values approached the entrainment limit, whereas no change in the duration of daily activity periods was found. No difference was observed between pre- and posttreatment values of the endogenous circadian period; hence, no aftereffects were found for any T value. These results indicate that the functional properties of entrainment to MEL are similar to those of entrainment to light, suggesting that both zeitgebers share a common timing mechanism.


Asunto(s)
Anticonvulsivantes/farmacología , Ritmo Circadiano/efectos de los fármacos , Ritmo Circadiano/fisiología , Melatonina/farmacología , Animales , Inyecciones Subcutáneas , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Long-Evans
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