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Jose Carlos Fernandes Galduroz - One of the best experts on this subject based on the ideXlab platform.
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effects of Biperiden cholinergic muscarinic m1 m4 receptor antagonist on ethanol conditioned place preference in mice
Neuroscience Letters, 2021Co-Authors: Paola Palombo, Sheila Antonagi Engi, Thais S Yokoyama, Andreia Gomes Bezerra, Daniela Fernandez Curado, Augusto Anesio, Rodrigo Molini Leao, Paulo Caleb Junior Lima Santos, Fabio C Cruz, Jose Carlos Fernandes GaldurozAbstract:Abstract Background Previous studies suggest that muscarinic cholinergic receptors might act upon the dopamine release in the mesolimbic system and alter drug-reinforcing values related to drug craving. Aims We examined the effects of systemic Biperiden administration, a muscarinic cholinergic (M1/M4) receptor antagonist, on ethanol (dose of 2 g/Kg) conditioned place preference (CPP), neuronal activation, dopamine and its metabolites levels in the nucleus accumbens. Methods Thirty minutes before the ethanol-induced CPP test, mice received saline or Biperiden at doses of 1.0, 5.0, or 10.0 mg/kg. The time spent in each compartment was recorded for 15 min. After the CPP protocol, animals were euthanized, and we investigated the activation of the nucleus accumbens by immunohistochemistry for Fos. We also quantified dopamine, homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens by high-performance liquid chromatography (HPLC). Additionally, the rotarod was employed to evaluate the effects of Biperiden on motor coordination. Results Biperiden at different doses (1.0, 5.0, and 10.0 mg/kg) blocked the expression of ethanol-induced CPP. These Biperiden doses increased the number of Fos-positive cells and the dopamine turnover in the nucleus accumbens. None of the doses affected the motor coordination evaluated by the rotarod. Conclusions Our results show that Biperiden can modulate the effect of alcohol reward, and its mechanism of action may involve a change in dopamine and cholinergic mesolimbic neurotransmission.
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Biperiden in the treatment of cocaine crack dependence clinical perspectives
The Neuroscience of Cocaine#R##N#Mechanisms and Treatment, 2017Co-Authors: Anna Carolina Ramos, Luiz Henrique Junqueira Dieckmann, Jose Carlos Fernandes GaldurozAbstract:Even though dopamine plays a central role in the reward system, other neurotransmitters are involved in the search for reinforcement. Cholinergic and dopaminergic systems together seem to coordinate the reinforcing function underlying drug consumption and addiction. Preclinical models including neurochemical and behavioral studies have shown effects of cholinergic agonists and antagonists on cocaine reinforcement. Recently, a double-blind placebo-controlled randomized study showed that Biperiden (a muscarinic antagonist) in addition to enhancing adherence to psychological therapy also reduced cocaine/crack craving and consumption. These results might be related to the cholinergic blockade that regulates the dopaminergic circuit in the nucleus accumbens and interferes with the learning processes and memory impairment by the administration of Biperiden. This damage could have a beneficial effect by dissociating the rewarding effects from the context.
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effects of Biperiden on the treatment of cocaine crack addiction a randomised double blind placebo controlled trial
European Neuropsychopharmacology, 2014Co-Authors: Luiz Henrique Junqueira Dieckmann, Anna Carolina Ramos, Eroy Aparecida Da Silva, Luis Pereira Justo, Pamela Sabioni, Iracema Francisco Frade, Altay Alves Lino De Souza, Jose Carlos Fernandes GaldurozAbstract:Cocaine use affects approximately 13.4 million people, or 0.3% of the world's population between 15 and 64 years of age. Several authors have described drug addiction as a disease of the brain reward system. Given that the cholinergic system impacts reward mechanisms and drug self-administration, acetylcholine (ACh) might play an important role in the cocaine addiction process. We evaluated the efficacy of Biperiden (a cholinergic antagonist) in reducing craving and the amount used, and in increasing compliance with treatment for cocaine/crack addiction. It was a study double-blind, randomised, placebo-controlled, 8-week trial of 111 cocaine or crack addicted male patients between 18 and 50 years old. Two groups were compared: placebo (n=55) or Biperiden (n=56) combined with weekly sessions of brief group cognitive-behavioural therapy. The efficacy of treatment was evaluated according to the patients' compliance and several instruments: the Minnesota Cocaine Craving Scale, the Beck Depression and Anxiety Scales and a questionnaire assessing the amount of drug used. All of the patients attended weekly sessions for two months. We analysed the data considering the patients' intention to treat based on our last observation. Of the 56 patients in the Biperiden group, 24 completed the treatment (42.8%) compared with only 11 patients in the placebo group (20%), which was a significant difference (p=0.009). Compliance with treatment was 118% higher in the Biperiden group, which was also the group that presented a statistically significant reduction in the amount of cocaine/crack use (p<0.001). There was statistically significant difference between the craving score in the Biperiden group. Pharmacological blockade of the cholinergic system with Biperiden is a promising alternative to treat cocaine/crack addiction, helping patients to reduce the amount used and improving compliance with psychotherapy treatment.
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Biperiden m1 antagonist impairs the expression of cocaine conditioned place preference but potentiates the expression of cocaine induced behavioral sensitization
Behavioural Brain Research, 2012Co-Authors: Anna Carolina Ramos, Monica L Andersen, Maria Gabriela Menezes Oliveira, Aline Da Costa Soeiro, Jose Carlos Fernandes GaldurozAbstract:Abstract Cocaine addiction is a public health issue in many countries, stressing the need for more effective treatments. As all drugs of abuse, cocaine acts on the brain reward system, increasing dopamine (DA) levels. Other neurotransmitters such as acetylcholine (ACh) are involved in the mechanisms underlying the development and the maintenance of cocaine addiction. ACh plays an important role in learning and memory processes and also regulates DA in some specific regions of the central nervous system. The present study investigated the effects of Biperiden, a muscarinic cholinergic (mACh) antagonist in two animal models: conditioned place preference (CPP) and behavioral sensitization. Male C57BL/6J mice were used in both studies. The CPP protocol was unbiased and carried out in three phases: habituation, conditioning and testing. For conditioning, cocaine was injected at a dose of 10 mg/kg in eight 15 min-sessions. The treatment with Biperiden (doses of 0.1, 1 and 10 mg/kg) was made 30 min prior to the testing session. For behavioral sensitization development, cocaine was administered at the dose of 10 mg/kg for 10 days. After sensitization, two challenges were performed: saline and cocaine (5 mg/kg). Biperiden (10 mg/kg) was administered 30 min before the cocaine challenge. At the dose of 10 mg/kg, Biperiden blocked the cocaine-CPP expression, suggesting an effect on conditioned memory retrieval. However, the same dose potentiated the expression of behavioral sensitization, suggesting an increase in DA release, probably in the NAc. Biperiden, as other mACh antagonists, may be a promising drug for the pharmacologic treatment of cocaine addiction.
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Biperiden an m1 antagonist reduces memory consolidation of cocaine conditioned place preference
Neuroscience Letters, 2012Co-Authors: Marina S Zacarias, Anna Carolina Ramos, Danielle R Alves, Jose Carlos Fernandes GaldurozAbstract:It is well-known that cocaine dependence is a public health issue, and several studies stress the need to look for new and more effective treatments. Although the mesolimbic dopamine (DA) system, which originates in the ventral tegmental area (VTA) and projects to several forebrain structures, is known to be critically involved in the neurobiology of cocaine dependence, acetylcholine (ACh) has also been shown to play an important role in cocaine dependence via its action on this reward system. ACh is also important in the formation of hippocampal memory associated with appetitive behavior. Thus, the aim of this study was to evaluate the effect of Biperiden, an ACh antagonist with high affinity for muscarinic M1 type receptors, on the acquisition of cocaine-conditioned place preference (CPP) in mice. The cocaine and Biperiden were dissolved in sterile saline and were administered intraperitoneally at a dose of 10mg/kg. The conditioning regime was 8 days long, and the cholinergic antagonist was given immediately at the end of each conditioning session. The test for CPP occurred 24h after the last session. The results showed that animals treated with Biperiden spent significantly less time in the cocaine-paired compartment than did the ones treated with saline. This finding represents a reduction in the consolidation of cocaine-induced CPP. One hypothesis that could explain this outcome focuses on the action of cholinergic antagonists on the consolidation of contextual memories. The amnesic effect of M1 antagonists on aversive tasks and on morphine CPP has been demonstrated when administered before the training or the conditioning session. The present study highlights the possibility of impairment in the acquisition of an appetitive memory, even when the cholinergic drug is administered after the conditioning session. This protocol also rejects the possibility of performance disturbance and suggests a possible pharmacological tool in the treatment of cocaine dependence.
Anke Sambeth - One of the best experts on this subject based on the ideXlab platform.
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Biperiden selectively impairs verbal episodic memory in a dose and time dependent manner in healthy subjects
Journal of Clinical Psychopharmacology, 2020Co-Authors: Laura Borghans, Anke Sambeth, Arjan BloklandAbstract:Purpose/Background: Biperiden is a muscarinic antagonist that produces memory impairments without impairing attention or motor functions in healthy subjects. It has been suggested that a Biperiden-induced memory deficit could model age- and dementia-related memory impairments. The goal of the current study was to determine the dose- and time-dependent effects of Biperiden on cognition in healthy volunteers. Methods/Procedures: Twenty-one healthy volunteers participated in a placebo-controlled, 3-way, crossover study. After a baseline test, cognitive performance was tested at 3 time points after a single dose of Biperiden 2 or 4 mg, or placebo. Episodic memory was measured using a 15-word verbal learning task (VLT). Furthermore, n-back tasks, a sustained attention to response task and a reaction time task were used, as well as subjective alertness and a side effects questionnaire. In addition, blood serum values and physiological measures were taken. Findings/Results: Biperiden decreased the number of words recalled in immediate and delayed recall of the VLT 90 minutes after drug intake. A dose-dependent impairment was found for the delayed recall, whereas the immediate recall was equally impaired by the 2 doses. Biperiden did not affect the performance on the VLT 4 hours after administration. Performance in the n-back task and the sustained attention to response task were not affected by Biperiden at any time point. Both doses were well tolerated as reported side effects were mild at Tmax and were minimal at the other time points. Implications/Conclusions: Biperiden exerts effects on episodic memory without negatively affecting other cognitive performance and behavioral measures that were assessed in this study. The data provide further evidence that Biperiden has selective effects on cognition, even after a high dose.
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the effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a Biperiden induced memory impairment
Psychopharmacology, 2018Co-Authors: Laura Borghans, Anke Sambeth, Jos Prickaerts, Johannes G Ramaekers, Arjan BloklandAbstract:After stimulation with nitric oxide, soluble guanylate cyclase (sGC) produces cyclic guanosine monophosphate (cGMP), which stimulates an important signalling pathway for long-term potentiation (LTP). By upregulating cGMP, LTP could be stimulated and thereby enhancing memory processes. The present study investigated the effects of the sGC stimulator riociguat on cognition in healthy volunteers. Participants were pre-treated with and without Biperiden, which impairs memory performance, to investigate the memory-enhancing effects of riociguat. Twenty volunteers participated in a double-blind placebo-controlled six-way crossover design with a cognitive test battery including the verbal learning task (VLT), n-back task, spatial memory test, the attention network test, and a reaction time task. Treatments were placebo and riociguat 0.5 mg, placebo and riociguat 1.0 mg, Biperiden 2.0 mg and placebo, Biperiden 2.0 mg and riociguat 0.5 mg and Biperiden 2.0 mg and riociguat 1.0 mg. Blood pressure was found to be decreased and heart rate to be increased after administration of riociguat. Cognitive performance was not enhanced after administration of riociguat. Biperiden decreased episodic memory on the VLT, yet this deficit was not reversed by riociguat. This supports the notion that Biperiden might be a valuable pharmacological model to induce episodic memory impairments as observed in AD/MCI.
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effects of Biperiden and acute tryptophan depletion and their combination on verbal word memory and eeg
Psychopharmacology, 2017Co-Authors: Laura Borghans, Arjan Blokland, Anke SambethAbstract:Research on the neurobiological foundations of memory has shown that multiple neurotransmitters play an important role in memory processing. To study the interaction between neurotransmitters such as acetylcholine and serotonin, pharmacological models can be used. In this study, we tested the effects of the muscarinic M1 antagonist Biperiden, acute tryptophan depletion (ATD), and the interaction between the two on episodic memory using the verbal learning task. The study was conducted according to a double-blind, placebo-controlled, four-way crossover design. Seventeen participants received Biperiden (2.0 mg), ATD (SolugelP), a combination of both, or a placebo in counterbalanced order with a wash out of at least 7 days. A verbal learning task was performed while recording electroencephalography. The task consisted of an immediate and delayed recall as well as a recognition part. Results revealed decreased scores on the delayed recall after Biperiden and ATD separately but no significant interaction between the two. However, the event-related potential components P3b, N400, and P600 did show an interaction during encoding. These results indicate that both BIP and ATD impair episodic memory. However, an interaction between the serotonergic and cholinergic system on memory performance is not supported.
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Biperiden selectively induces memory impairment in healthy volunteers no interaction with citalopram
Psychopharmacology, 2015Co-Authors: Anke Sambeth, W J Riedel, Inge Klinkenberg, Seppo Kahkonen, Arjan BloklandAbstract:Traditionally, the non-selective muscarinic antagonist scopolamine has been used to induce episodic memory impairments as found in Alzheimer’s disease (AD). However, it also impairs attention and induces drowsiness. Muscarinic antagonists more selective for the M1 receptor might, therefore, be preferred. We examined the effects of the M1 antagonist Biperiden on cognitive functions in order to test the specificity of this drug on memory performance. Additionally, we assessed whether the selective serotonin re-uptake inhibitor citalopram can reverse a possible Biperiden-induced impairment. The study was conducted according to a double-blind, placebo-controlled, four-way cross-over design. Sixteen volunteers received Biperiden (2 mg), citalopram (20 mg), a combination of the two, or a placebo in counterbalanced order with a washout of at least 4 days. Cognitive tests (verbal memory, continuous recognition memory, spatial memory, choice reaction) were performed 4 and 1 h after treatment with citalopram and Biperiden, respectively. Biperiden impaired memory performance in the verbal learning task, the continuous recognition memory test, and the spatial memory task. Effects on attention and side effects, as measured using the choice reaction time test and questionnaires respectively, could be neglected. Citalopram did not affect any of the memory or attention measures taken. Most importantly, citalopram was also unable to reverse the Biperiden-induced memory impairments. Our results, thus, show that the M1 antagonist Biperiden may serve as a translational model to induce episodic memory deficits as seen in AD. However, the interactive influence of acetylcholine and serotonin on memory could not be confirmed.
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human electrophysiological correlates of learned irrelevance effects of the muscarinic m1 antagonist Biperiden
The International Journal of Neuropsychopharmacology, 2012Co-Authors: Inge Klinkenberg, W J Riedel, Arjan Blokland, Anke SambethAbstract:Learned irrelevance (LIrr) refers to a reduction in associative learning after pre-exposure of the conditioned and unconditioned stimulus in a non-contingent fashion. This paradigm might serve as a translational model for (pre)attentive information processing deficits in schizophrenia. This is the first study to investigate the event-related potentials (ERPs) of a within-subject LIrr paradigm in humans. Furthermore, the effects of the muscarinic M1 antagonist Biperiden on LIrr were assessed. As expected, LIrr was found to be intact in young healthy volunteers after placebo. Furthermore, in the placebo condition P3b latency was decreased for target stimuli, which were pre-cued. This suggests that the predictability of the occurrence of these stimuli is mainly reflected by this ERP component. Biperiden had no effect on the behavioural LIrr measures, although prolonged reaction times were evident. Biperiden increased the N1 amplitude of the pre-exposed predictor letters, suggesting an effect of this drug on early perceptual processing. In conclusion, the within-subject paradigm used in the current study in combination with electroencephalography can reveal brain mechanisms involved in LIrr. M1 antagonism did not affect LIrr performance but seemed to influence early information processing.
Christian J Gillin - One of the best experts on this subject based on the ideXlab platform.
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no antidepressant effect of Biperiden compared with placebo in depression a double blind 6 week clinical trial
Psychiatry Research-neuroimaging, 1995Co-Authors: Christian J Gillin, John Lauriello, John R Kelsoe, Mark Hyman Rapaport, Shahrokh Golshan, William M Kenny, Laura SuttonAbstract:Abstract Depression may result from an increased ratio of cholinergic to aminergic central neurotransmission. The effect of centrally active anticholinergic agents on depressive ratings in depressed patients, however, has not been well studied. In a previous open label 4-week clinical trial, Kasper et al. (1981) reported that Biperiden (Akineton) had antidepressant effects in depressed patients. We compared the effects of placebo and Biperiden in a randomized, double-blind, parallel-design 6-week study. All patients received placebo for the first week and then received either Biperiden (≤ 12 mg/day) or a peripherally acting anticholinergic agent, glycopyrrolate (Robinul, 1 mg/day) for 4 weeks. All patients received placebo during week 6. Both groups significantly improved, but Biperiden did not demonstrate any significant benefit compared with glycopyrrolate. In a subgroup of patients receiving Biperiden, the percentage of rapid eye movement sleep was significantly decreased only in the first week of Biperiden compared with the initial placebo week, suggesting that tolerance to the central effects of Biperiden developed. Further studies would be needed to determine whether anticholinergic agents possess antidepressant properties.
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development of tolerance after repeated administration of a selective muscarinic m1 antagonist Biperiden in healthy human volunteers
Biological Psychiatry, 1993Co-Authors: Estela Nieves, Rafael J Salinpascual, Daniel Granadosfuentes, Lourdes Galiciapolo, Christian J GillinAbstract:The muscarinic antagonist Biperiden produces a dose-dependent inhibition of (REM) sleep on acute administration. The present study addressed the possibility of pharmacological tolerance after repeated Biperiden administration. Six healthy volunteers were studied under sleep laboratory conditions in the following situations: one acclimatization, night, two baseline (that were averaged), 4 nights of Biperiden administration, and 4 nights of placebo recovery administration. Six milligrams of Biperiden and placebo were administered in identical capsules. Volunteers and technicians were blind to the order of the administration of the capsules. REM sleep time was reduced during the first and the second night, but was not significantly different in comparison with baseline by the third night. During placebo recovery nights, REM sleep time was not different from baseline. REM sleep latency was increased during the first and second nights of Biperiden administration, but tolerance to this effect was observed by the third night. On placebo nights a dramatic shortening of REM latency was observed. The present findings support the hypothesis that anticholinergic drugs, even a selective M1 antagonist such as Biperiden, induce tolerance soon after administration. A similar effect has been reported with scopolamine, a nonselective muscarinic antagonist, but the main difference is that Biperiden withdrawal was not followed by an REM sleep rebound. The observed effect on REM sleep latency during placebo administration may be related to a supersensitivity to muscarinic M-1 receptors that trigger the first REM sleep period. Because short REM latency has been the main finding in the sleep of depressed patients, some implications of the present findings are discussed.
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dose dependent inhibition of rem sleep in normal volunteers by Biperiden a muscarinic antagonist
Biological Psychiatry, 1991Co-Authors: Christian J Gillin, Shahrokh Golshan, Laura Sutton, Caroline Ruiz, Sharon HirschAbstract:We tested the effect of Biperiden (2, 4, and 8 mg per os 30 min before bedtime) on the polygraphically recorded sleep of normal volunteers (n = 8). Biperiden is a cholinergic, muscarinic receptor antagonist that may preferentially block the M1 receptor subtype. Compared with placebo, Biperiden significantly prolonged rapid eye movement (REM) latency and suppressed REM sleep time and REM percentage in a dose-dependent manner. These REM suppressing effects of Biperiden are similar to those previously reported with scopolamine and other nonselective muscarinic receptor antagonists. Because of uncertainties about the pharmacological specificity of Biperiden, further studies are needed to determine the mechanism of action and the role of M1 receptors subtypes in the regulation of REM sleep.
Arjan Blokland - One of the best experts on this subject based on the ideXlab platform.
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Biperiden selectively impairs verbal episodic memory in a dose and time dependent manner in healthy subjects
Journal of Clinical Psychopharmacology, 2020Co-Authors: Laura Borghans, Anke Sambeth, Arjan BloklandAbstract:Purpose/Background: Biperiden is a muscarinic antagonist that produces memory impairments without impairing attention or motor functions in healthy subjects. It has been suggested that a Biperiden-induced memory deficit could model age- and dementia-related memory impairments. The goal of the current study was to determine the dose- and time-dependent effects of Biperiden on cognition in healthy volunteers. Methods/Procedures: Twenty-one healthy volunteers participated in a placebo-controlled, 3-way, crossover study. After a baseline test, cognitive performance was tested at 3 time points after a single dose of Biperiden 2 or 4 mg, or placebo. Episodic memory was measured using a 15-word verbal learning task (VLT). Furthermore, n-back tasks, a sustained attention to response task and a reaction time task were used, as well as subjective alertness and a side effects questionnaire. In addition, blood serum values and physiological measures were taken. Findings/Results: Biperiden decreased the number of words recalled in immediate and delayed recall of the VLT 90 minutes after drug intake. A dose-dependent impairment was found for the delayed recall, whereas the immediate recall was equally impaired by the 2 doses. Biperiden did not affect the performance on the VLT 4 hours after administration. Performance in the n-back task and the sustained attention to response task were not affected by Biperiden at any time point. Both doses were well tolerated as reported side effects were mild at Tmax and were minimal at the other time points. Implications/Conclusions: Biperiden exerts effects on episodic memory without negatively affecting other cognitive performance and behavioral measures that were assessed in this study. The data provide further evidence that Biperiden has selective effects on cognition, even after a high dose.
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the effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a Biperiden induced memory impairment
Psychopharmacology, 2018Co-Authors: Laura Borghans, Anke Sambeth, Jos Prickaerts, Johannes G Ramaekers, Arjan BloklandAbstract:After stimulation with nitric oxide, soluble guanylate cyclase (sGC) produces cyclic guanosine monophosphate (cGMP), which stimulates an important signalling pathway for long-term potentiation (LTP). By upregulating cGMP, LTP could be stimulated and thereby enhancing memory processes. The present study investigated the effects of the sGC stimulator riociguat on cognition in healthy volunteers. Participants were pre-treated with and without Biperiden, which impairs memory performance, to investigate the memory-enhancing effects of riociguat. Twenty volunteers participated in a double-blind placebo-controlled six-way crossover design with a cognitive test battery including the verbal learning task (VLT), n-back task, spatial memory test, the attention network test, and a reaction time task. Treatments were placebo and riociguat 0.5 mg, placebo and riociguat 1.0 mg, Biperiden 2.0 mg and placebo, Biperiden 2.0 mg and riociguat 0.5 mg and Biperiden 2.0 mg and riociguat 1.0 mg. Blood pressure was found to be decreased and heart rate to be increased after administration of riociguat. Cognitive performance was not enhanced after administration of riociguat. Biperiden decreased episodic memory on the VLT, yet this deficit was not reversed by riociguat. This supports the notion that Biperiden might be a valuable pharmacological model to induce episodic memory impairments as observed in AD/MCI.
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effects of Biperiden and acute tryptophan depletion and their combination on verbal word memory and eeg
Psychopharmacology, 2017Co-Authors: Laura Borghans, Arjan Blokland, Anke SambethAbstract:Research on the neurobiological foundations of memory has shown that multiple neurotransmitters play an important role in memory processing. To study the interaction between neurotransmitters such as acetylcholine and serotonin, pharmacological models can be used. In this study, we tested the effects of the muscarinic M1 antagonist Biperiden, acute tryptophan depletion (ATD), and the interaction between the two on episodic memory using the verbal learning task. The study was conducted according to a double-blind, placebo-controlled, four-way crossover design. Seventeen participants received Biperiden (2.0 mg), ATD (SolugelP), a combination of both, or a placebo in counterbalanced order with a wash out of at least 7 days. A verbal learning task was performed while recording electroencephalography. The task consisted of an immediate and delayed recall as well as a recognition part. Results revealed decreased scores on the delayed recall after Biperiden and ATD separately but no significant interaction between the two. However, the event-related potential components P3b, N400, and P600 did show an interaction during encoding. These results indicate that both BIP and ATD impair episodic memory. However, an interaction between the serotonergic and cholinergic system on memory performance is not supported.
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Biperiden selectively induces memory impairment in healthy volunteers no interaction with citalopram
Psychopharmacology, 2015Co-Authors: Anke Sambeth, W J Riedel, Inge Klinkenberg, Seppo Kahkonen, Arjan BloklandAbstract:Traditionally, the non-selective muscarinic antagonist scopolamine has been used to induce episodic memory impairments as found in Alzheimer’s disease (AD). However, it also impairs attention and induces drowsiness. Muscarinic antagonists more selective for the M1 receptor might, therefore, be preferred. We examined the effects of the M1 antagonist Biperiden on cognitive functions in order to test the specificity of this drug on memory performance. Additionally, we assessed whether the selective serotonin re-uptake inhibitor citalopram can reverse a possible Biperiden-induced impairment. The study was conducted according to a double-blind, placebo-controlled, four-way cross-over design. Sixteen volunteers received Biperiden (2 mg), citalopram (20 mg), a combination of the two, or a placebo in counterbalanced order with a washout of at least 4 days. Cognitive tests (verbal memory, continuous recognition memory, spatial memory, choice reaction) were performed 4 and 1 h after treatment with citalopram and Biperiden, respectively. Biperiden impaired memory performance in the verbal learning task, the continuous recognition memory test, and the spatial memory task. Effects on attention and side effects, as measured using the choice reaction time test and questionnaires respectively, could be neglected. Citalopram did not affect any of the memory or attention measures taken. Most importantly, citalopram was also unable to reverse the Biperiden-induced memory impairments. Our results, thus, show that the M1 antagonist Biperiden may serve as a translational model to induce episodic memory deficits as seen in AD. However, the interactive influence of acetylcholine and serotonin on memory could not be confirmed.
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human electrophysiological correlates of learned irrelevance effects of the muscarinic m1 antagonist Biperiden
The International Journal of Neuropsychopharmacology, 2012Co-Authors: Inge Klinkenberg, W J Riedel, Arjan Blokland, Anke SambethAbstract:Learned irrelevance (LIrr) refers to a reduction in associative learning after pre-exposure of the conditioned and unconditioned stimulus in a non-contingent fashion. This paradigm might serve as a translational model for (pre)attentive information processing deficits in schizophrenia. This is the first study to investigate the event-related potentials (ERPs) of a within-subject LIrr paradigm in humans. Furthermore, the effects of the muscarinic M1 antagonist Biperiden on LIrr were assessed. As expected, LIrr was found to be intact in young healthy volunteers after placebo. Furthermore, in the placebo condition P3b latency was decreased for target stimuli, which were pre-cued. This suggests that the predictability of the occurrence of these stimuli is mainly reflected by this ERP component. Biperiden had no effect on the behavioural LIrr measures, although prolonged reaction times were evident. Biperiden increased the N1 amplitude of the pre-exposed predictor letters, suggesting an effect of this drug on early perceptual processing. In conclusion, the within-subject paradigm used in the current study in combination with electroencephalography can reveal brain mechanisms involved in LIrr. M1 antagonism did not affect LIrr performance but seemed to influence early information processing.
Rafael J Salinpascual - One of the best experts on this subject based on the ideXlab platform.
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development of tolerance after repeated administration of a selective muscarinic m1 antagonist Biperiden in healthy human volunteers
Biological Psychiatry, 1993Co-Authors: Estela Nieves, Rafael J Salinpascual, Daniel Granadosfuentes, Lourdes Galiciapolo, Christian J GillinAbstract:The muscarinic antagonist Biperiden produces a dose-dependent inhibition of (REM) sleep on acute administration. The present study addressed the possibility of pharmacological tolerance after repeated Biperiden administration. Six healthy volunteers were studied under sleep laboratory conditions in the following situations: one acclimatization, night, two baseline (that were averaged), 4 nights of Biperiden administration, and 4 nights of placebo recovery administration. Six milligrams of Biperiden and placebo were administered in identical capsules. Volunteers and technicians were blind to the order of the administration of the capsules. REM sleep time was reduced during the first and the second night, but was not significantly different in comparison with baseline by the third night. During placebo recovery nights, REM sleep time was not different from baseline. REM sleep latency was increased during the first and second nights of Biperiden administration, but tolerance to this effect was observed by the third night. On placebo nights a dramatic shortening of REM latency was observed. The present findings support the hypothesis that anticholinergic drugs, even a selective M1 antagonist such as Biperiden, induce tolerance soon after administration. A similar effect has been reported with scopolamine, a nonselective muscarinic antagonist, but the main difference is that Biperiden withdrawal was not followed by an REM sleep rebound. The observed effect on REM sleep latency during placebo administration may be related to a supersensitivity to muscarinic M-1 receptors that trigger the first REM sleep period. Because short REM latency has been the main finding in the sleep of depressed patients, some implications of the present findings are discussed.
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Biperiden administration in normal sleep and after rapid eye movement sleep deprivation in healthy volunteers
Neuropsychopharmacology, 1991Co-Authors: Rafael J Salinpascual, Estela Nieves, Daniel Granadosfuentes, Lourdes Galiciapolo, J EcheverryAbstract:Twenty-six healthy volunteers were randomly assigned to one of four groups. Groups Bip-4 and Bip-6, each with six subjects, received 4 and 6 mg of Biperiden, respectively, and were studied on acclimatization, baseline, Biperiden, and follow-up nights. Group REM-P (n = 7) and Group REM-Bip (n = 7) were studied on acclimatization, baseline, six nights of REM sleep deprivation, and one recovery (treatment) night with either placebo (group REM-P) or Biperiden (group REM-Bip), and one follow-up night. Biperiden 4 and 6 mg increased REM sleep latency and Biperiden 6 mg reduced REM sleep time. On the recovery night following REM sleep deprivation Group REM-P and REM-Bip showed an increase in sleep continuity. REM sleep time in the REM-P group was increased during the recovery (treatment) night (REM sleep recovery), while the REM-Bip group did not show a significant REM sleep increase during recovery (treatment) night. It was not until the follow-up night that REM sleep increased in the REM-Bip group.