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2.
Addict Biol ; 27(1): e13094, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34463411

RESUMO

Stimulant drug-paired cues can acquire the ability to activate mesocorticolimbic pathways and lead to new bouts of drug use. Studies in laboratory animals suggest that these effects are augmented by progressively greater drug use histories, impulsive personality traits, and acute drug ingestion. As a preliminary test of these hypotheses in humans, we exposed cocaine users (n = 14) and healthy volunteers (n = 10) to cocaine-related videos during two functional magnetic resonance imaging (fMRI) sessions, once following acute administration of placebo and once following d-amphetamine (0.3 mg/kg, p.o.). Across sessions, cocaine users showed larger cocaine cue-induced responses than healthy controls in the associative striatum and midbrain. Among the cocaine users, larger drug cue-induced responses during the placebo session were correlated with higher Barratt Impulsiveness Scale (BIS-11) nonplanning scores (associative striatum) and greater lifetime use of stimulant drugs (limbic, associative, and sensorimotor striatum). The administration of d-amphetamine did not augment the cue-induced activations, but, in cocaine users, drug cue-induced striatal activations were more widespread following prolonged cocaine cue exposure. Together, these effects of past and present drug use might aggravate the risk for stimulant drug use problems.


Assuntos
Encéfalo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/patologia , Cocaína/farmacologia , Sinais (Psicologia) , Comportamento Impulsivo/efeitos dos fármacos , Adulto , Encéfalo/diagnóstico por imagem , Fissura/efeitos dos fármacos , Dextroanfetamina/farmacologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino
3.
BMC Psychiatry ; 18(1): 68, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29548306

RESUMO

BACKGROUND: Some authors have hypothesized that Treatment-Resistant Unipolar Depression (TRD-UP) should be considered within the bipolar spectrum disorders and that hidden bipolarity may be a risk factor for TRD-UP. However, there are neither studies comparing clinical and sociodemographic data of patients with TRD-UP versus Bipolar (BP) disorders nor are there any examining differences versus Bipolar type I (BP-I) and Bipolar type II (BP-II). METHODS: Charts analysis was conducted on 194 patients followed at the Mood Disorders Clinic of the McGill University Health Center. Sociodemographic, clinical features and depression scales were collected from patients meeting DSM-IV criteria for TRD-UP (n = 100) and BP (n = 94). Binary logistic regression analysis was conducted to examine clinical predictors independently associated with the two disorders. RESULTS: Compared to BP, TRD-UP patients exhibited greater severity of depression, prevalence of anxiety and panic disorders, melancholic features, Cluster-C personality disorders, later onset of depression and fewer hospitalizations. Binary logistic regression indicated that higher comorbidity with anxiety disorders, higher depression scale scores and lower global assessment of functioning (GAF) scores, and lower number of hospitalizations and psychotherapies differentiated TRD-UP from BP patients. We also found that the rate of unemployment and the number of hospitalizations for depression was higher in BP-I than in BP-II, while the rate of suicide attempts was lower in BP-I than in BP-II depressed patients. CONCLUSIONS: These results suggest that TRD-UP constitutes a distinct psychopathological condition and not necessarily a prodromal state of BP depression.


Assuntos
Transtorno Bipolar/epidemiologia , Transtorno Depressivo Resistente a Tratamento/epidemiologia , Adulto , Idoso , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Quebeque/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
4.
Int Clin Psychopharmacol ; 33(1): 34-43, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28906325

RESUMO

Patients with treatment-resistant unipolar depression (TRD) are treated with antidepressant combinations (ADs) or with second-generation antipsychotics plus AD (SGA+AD) augmentation; however, the clinical characteristics, the factors associated independently with response to SGA+AD, and the outcome trajectories have not yet been characterized. We performed a naturalistic study on the latest stable trial (medication unchanged for about 3 months) in 86 TRD patients with resistance to at least two ADs trials, who received ADs (n=36) or SGA+AD (n=50) treatments. Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton-Depression Rating Scale (HAM-D17), and other scales were administered before (T0) and after the latest 3-month stable trial (T3). Compared to ADs, the SGA+AD group showed increased percentage of depression with psychotic features, comorbidity for personality disorders and substance use disorders (SUD), higher number of failed ADs pharmacotherapies and depressive symptoms at T0 on all scales (P<0.001). Compared to T0, both treatments significantly decreased depressive symptoms on MADRS and HAM-D17 at T3 (P<0.001); however, the SGA+AD augmentation produced a greater decline in mean score. Logistic regression analysis indicated that psychotic features, personality disorders, and SUD were independently associated with SGA+AD treatment. Given the greater improvement in depression following SGA+AD augmentation, SGA augmentation should be indicated as a first-line treatment in severe TRD with psychotic features, SUD, and personality disorders.


Assuntos
Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo Resistente a Tratamento/psicologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
Sci Rep ; 7: 46665, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28443614

RESUMO

It has been proposed that the acquisition of drug seeking is related to the development of conditioned dopamine responses in the ventral striatum. As drug use continues and becomes habit-like, conditioned responses have been shown to shift to the dorsal striatum. Here, using the PET [11C]raclopride method and highly personalized cocaine cues, we report the first evidence in humans of the dorsal dopamine response prior to the onset of addiction.


Assuntos
Cocaína/farmacologia , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Comportamento de Procura de Droga/efeitos dos fármacos , Adolescente , Adulto , Comportamento Aditivo/diagnóstico por imagem , Radioisótopos de Carbono/química , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/metabolismo , Sinais (Psicologia) , Inibidores da Captação de Dopamina/farmacologia , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Racloprida/química , Inquéritos e Questionários , Adulto Jovem
6.
J Neurotrauma ; 32(1): 38-44, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24955920

RESUMO

Mild traumatic brain injury (mTBI) is typically followed by various postconcussive symptoms (PCS), including headache, depression, and cognitive deficits. In 15-25% of cases, PCS persists beyond the usual 3-month recovery period, interfering with activities of daily living and responding poorly to pharmacotherapy. We tested the safety, tolerability, and efficacy of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for alleviating PCS. Fifteen eligible patients with mTBI and PCS > 3 months postinjury consented to 20 sessions of rTMS (20 × 5-sec trains; 10 Hz at 110% threshold), with clinical and functional magnetic resonance imaging (fMRI) assessments before and after intervention and clinical assessment at 3-month follow-up. Primary outcomes were tolerability, safety, and efficacy, as measured with the PCS Scale. Secondary outcomes included the Cognitive Symptoms Questionnaire, neuropsychological test performance, and working memory task-associated activity as assessed with fMRI. Twelve patients completed all sessions. Three withdrew because of worsening symptoms or for an unrelated event. Stimulation intensity was increased gradually across sessions, and all subjects tolerated the protocol by the sixth session. Commonly reported side effects among completers were increased headache (n = 3) and greater sleep disturbance (n = 3). Participants also reported positive outcomes such as less sleep disturbance (n = 3), and better mental focus (n = 3). On average, PCS scores declined by 14.6 points (p = 0.009) and fMRI task-related activation peaks in the DLPFC increased after rTMS. rTMS is safe, tolerated by most patients with mTBI, and associated with both a reduction in severity of PCS and an increase in task-related activations in DLPFC. Assessment of this intervention in a randomized, control trial is warranted.


Assuntos
Atividades Cotidianas/psicologia , Lesões Encefálicas/complicações , Memória de Curto Prazo , Síndrome Pós-Concussão/terapia , Córtex Pré-Frontal/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adulto , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/psicologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Testes Neuropsicológicos , Síndrome Pós-Concussão/etiologia , Síndrome Pós-Concussão/psicologia , Resultado do Tratamento , Adulto Jovem
7.
Ther Adv Psychopharmacol ; 4(6): 257-67, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25489477

RESUMO

BACKGROUND: Physicians have prescribed anticholinergic agents such as benztropine, procyclidine, biperiden and trihexyphenidyl for treatment and prophylaxis of antipsychotic-induced extrapyramidal symptoms (EPS) for decades. Anticholinergic agents can however worsen tardive dyskinesia and cause many adverse effects, including cognitive impairment. Previous studies of anticholinergic discontinuation in patients with schizophrenia receiving antipsychotics have yielded a wide range of EPS relapse rates. Improvement in cognition after anticholinergic withdrawal was observed in some studies. OBJECTIVE: This study evaluated the effect of anticholinergic discontinuation on movement disorders, cognition and general psychopathology after a 4-week taper in 20 outpatients with schizophrenia or schizoaffective disorder treated with antipsychotics. RESULTS: Eighteen of twenty patients successfully discontinued their anticholinergic medication; two did not because of akathisia. Repeated measures analysis of variance did not show a significant effect of anticholinergic discontinuation on total Extrapyramidal Symptoms Rating Scale score or on the Parkinsonism, Akathisia, Dystonia or Tardive Dyskinesia subscales. However, significant improvement was found on the Brief Assessment of Cognition in Schizophrenia composite z score at weeks 6, 8 and 12 compared with baseline. Significant improvements were seen on the motor and the symbol-coding tasks. No significant effects were observed on the Positive and Negative Syndrome Scale, Clinical Global Impression - Severity and Clinical Global Impression - Improvement scales. CONCLUSION: In this 12-week study of anticholinergic discontinuation in 20 outpatients with schizophrenia or schizoaffective disorder, gradual decrease and discontinuation of anticholinergics led to a positive effect on cognition. There were no adverse consequences on general psychopathology and no significant differences for 18 of 20 subjects on movement disorders.

8.
J Neurosurg ; 116(2): 315-22, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22098195

RESUMO

OBJECT: Deep brain stimulation (DBS) has been recently investigated as a treatment for major depression. One of the proposed targets for this application is the subcallosal cingulate gyrus (SCG). To date, promising results after SCG DBS have been reported by a single center. In the present study the authors investigated whether these findings may be replicated at different institutions. They conducted a 3-center prospective open-label trial of SCG DBS for 12 months in patients with treatment-resistant depression. METHODS: Twenty-one patients underwent implantation of bilateral SCG electrodes. The authors examined the reduction in Hamilton Rating Scale for Depression (HRSD-17) score from baseline (RESP50). RESULTS: Patients treated with SCG DBS had an RESP50 of 57% at 1 month, 48% at 6 months, and 29% at 12 months. The response rate after 12 months of DBS, however, increased to 62% when defined as a reduction in the baseline HRSD-17 of 40% or more. Reductions in depressive symptomatology were associated with amelioration in disease severity in patients who responded to surgery. CONCLUSIONS: Overall, findings from this study corroborate the results of previous reports showing that outcome of SCG DBS may be replicated across centers.


Assuntos
Estimulação Encefálica Profunda/métodos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Giro do Cíngulo/fisiologia , Adulto , Antidepressivos/uso terapêutico , Corpo Caloso , Estimulação Encefálica Profunda/efeitos adversos , Estimulação Encefálica Profunda/normas , Transtorno Depressivo Maior/tratamento farmacológico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Br J Psychiatry ; 199(5): 391-7, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21543823

RESUMO

BACKGROUND: Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits. AIMS: To investigate the effects of lowered serotonin on cocaine-induced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving. METHOD: In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [(11)C]raclopride. RESULTS: Acute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine. CONCLUSIONS: The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/metabolismo , Cocaína/farmacologia , Corpo Estriado/metabolismo , Inibidores da Captação de Dopamina/farmacologia , Dopamina/metabolismo , Serotonina/metabolismo , Administração Intranasal , Adulto , Análise de Variância , Cocaína/administração & dosagem , Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Transtornos Relacionados ao Uso de Cocaína/psicologia , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/efeitos dos fármacos , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons/métodos , Racloprida/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Triptofano/administração & dosagem , Triptofano/deficiência , Triptofano/metabolismo , Adulto Jovem
12.
Biol Psychiatry ; 65(10): 846-50, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19249751

RESUMO

BACKGROUND: The effect of self-administered cocaine on extracellular dopamine (DA) levels has not been measured in humans. METHODS: Ten nondependent cocaine users underwent positron emission tomography [11C]raclopride scans following intranasal self-administration of cocaine hydrochloride (1.0 mg/kg) and placebo powder. RESULTS: Compared with placebo, intranasal cocaine self-administration decreased [11C]raclopride binding values in the ventral limbic striatum and putamen. Individual differences in the magnitude of the [11C]raclopride response in the ventral striatum were predicted by lifetime histories of stimulant drug use. CONCLUSIONS: The results suggest that 1) intranasal cocaine self-administration increases synaptic DA levels in human striatum and 2) prior use of stimulant drugs on the street is associated with progressively greater cocaine-induced DA responses. These dopaminergic effects might influence susceptibility to drug-seeking behavior and the progression to substance abuse.


Assuntos
Administração Intranasal , Gânglios da Base/metabolismo , Cocaína/administração & dosagem , Cocaína/farmacologia , Dopamina/metabolismo , Gânglios da Base/diagnóstico por imagem , Cocaína/farmacocinética , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Fenilalanina/sangue , Tomografia por Emissão de Pósitrons , Putamen/diagnóstico por imagem , Putamen/metabolismo , Racloprida/administração & dosagem , Racloprida/metabolismo , Receptores de Dopamina D2/metabolismo , Autoadministração , Tirosina/sangue , Adulto Jovem
13.
Can J Clin Pharmacol ; 13(1): e69-74, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16456219

RESUMO

OBJECTIVE: To describe tardive rebound anxiety phenomena (panic, anxiety and insomnia) following abrupt paroxetine discontinuation. METHOD: Case report, with comprehensive literature review on rebound and withdrawal phenomena associated with psychotropic medications. RESULTS: Three different discontinuation syndromes with psychotropics are described: (1) new-onset CNS-depressant type withdrawal symptoms (minor and major); (2) rebound syndromes; and (3) supersensitivity symptoms. Abrupt paroxetine discontinuation has been well described and fits the first category. Tardive rebound panic disorder-phenomena with paroxetine has some features of the supersensitivity category. CONCLUSION: Chronic paroxetine treatment may lead to 5-HT2-receptor down regulation, with desensitization of 5-HT1A and 5-HT2 receptors, which may contribute to tardive rebound symptoms upon abrupt withdrawal. Early reports suggest that genetic factors may also contribute to withdrawal symptoms in susceptible individuals. Cholinergic rebound may also occur and could explain tardive insomnia and anxiety in paroxetine withdrawal.


Assuntos
Ansiedade/diagnóstico , Transtorno de Pânico/diagnóstico , Paroxetina/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Síndrome de Abstinência a Substâncias/diagnóstico , Idoso , Acatisia Induzida por Medicamentos/diagnóstico , Acatisia Induzida por Medicamentos/psicologia , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Feminino , Humanos , Transtorno de Pânico/induzido quimicamente , Transtorno de Pânico/psicologia , Paroxetina/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/psicologia , Síndrome de Abstinência a Substâncias/psicologia
14.
Can J Psychiatry ; 50(11): 703-14, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16363464

RESUMO

OBJECTIVE: Tardive dyskinesia (TD), the principal adverse effect of long-term conventional antipsychotic treatment, can be debilitating and, in many cases, persistent. We sought to explore the incidence and management of TD in the era of atypical antipsychotics because it remains an important iatrogenic adverse effect. METHODS: We conducted a review of TD incidence and management literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, management, therapy, neuroleptics, antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Additional articles were obtained by searching the bibliographies of relevant references. We considered articles that contributed to the current understanding of both the incidence of TD with atypical antipsychotics and management strategies for TD. RESULTS: The incidence of TD is significantly lower with atypical, compared with typical, antipsychotics, but cases of de novo TD have been identified. Evidence suggests that atypical antipsychotic therapy ameliorates long-standing TD. This paper outlines management strategies for TD in patients with schizophrenia. CONCLUSION: The literature supports the recommendation that atypical antipsychotics should be the first antipsychotics used in patients who have experienced TD as a result of treatment with conventional antipsychotic agents. The other management strategies discussed may prove useful in certain patients.


Assuntos
Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/etiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Antipsicóticos/uso terapêutico , Aripiprazol , Benzodiazepinas/efeitos adversos , Clozapina/efeitos adversos , Dibenzotiazepinas/efeitos adversos , Humanos , Incidência , Olanzapina , Piperazinas/efeitos adversos , Fumarato de Quetiapina , Quinolonas/efeitos adversos , Risperidona/efeitos adversos , Tiazóis/efeitos adversos
15.
Can J Psychiatry ; 50(9): 541-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16262110

RESUMO

OBJECTIVE: Tardive dyskinesia (TD) is the principal adverse effect of long-term treatment with conventional antipsychotic agents. Several mechanisms may exist for this phenomenon. Mechanisms for the lower incidence of TD with atypical antipsychotics also remain to be fully understood. We undertook to explore and better understand these mechanisms. METHODS: We conducted a comprehensive review of TD pathophysiology literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, neuroleptics, antipsychotics, pathophysiology, and mechanisms. Additional articles were obtained by searching the bibliographies of relevant references. Articles were considered if they contributed to the current understanding of the pathophysiology of TD. RESULTS: Current TD vulnerability models include genetic vulnerability, disease-related vulnerability, and decreased functional reserve. Mechanisms of TD induction include prolonged blockade of postsynaptic dopamine receptors, postsynaptic dopamine hypersensitivity, damage to striatal GABA interneurons, and damage of striatal cholinergic interneurons. Atypical antipsychotics may cause less TD because they have less impact on the basal ganglia and are less likely to cause postsynaptic dopamine hypersensitivity. CONCLUSION: Although the ultimate model for TD is not yet understood, it is plausible that several of these vulnerabilities and mechanisms act together to produce TD. The lower incidence of TD with atypical antipsychotics has helped to elucidate the,mechanisms of TD.


Assuntos
Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/etiologia , Discinesia Induzida por Medicamentos/fisiopatologia , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Fibras Colinérgicas/efeitos dos fármacos , Fibras Colinérgicas/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Humanos , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Receptores de GABA/efeitos dos fármacos , Receptores de GABA/metabolismo , Serotonina/metabolismo
16.
Behav Neurosci ; 119(6): 1619-27, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16420164

RESUMO

The authors used the acute phenylalanine-tyrosine depletion (APTD) method to test the effect of transient catecholamine precursor depletion on cocaine craving, euphoria, and self-administration. Eight nondependent, nontreatment-seeking cocaine users self-administered 3 doses of cocaine (0.6, 1.5, 3.0 mg/kg, taken intranasally) following ingestion of (a) a nutritionally balanced amino acid mixture, (b) APTD, and (c) APTD followed by L-dopa/carbidopa (2x100 mg/25 mg). APTD decreased both cue and cocaine-induced drug craving but not euphoria or self-administration. APTD+L-dopa also decreased drug craving, possibly reflecting the ability of L-dopa to transiently decrease dopamine cell firing. Together, these preliminary results suggest that the craving elicited by cocaine and cocaine cues is related to changes in catecholamine neurotransmission. Euphoria and the self-administration of freely available drugs by regular users, in comparison, might be better accounted for by other mechanisms.


Assuntos
Catecolaminas/deficiência , Transtornos Relacionados ao Uso de Cocaína/psicologia , Cocaína/administração & dosagem , Inibidores da Captação de Dopamina/administração & dosagem , Euforia/efeitos dos fármacos , Adulto , Catecolaminas/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Cocaína/sangue , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dieta com Restrição de Proteínas , Dopaminérgicos/uso terapêutico , Inibidores da Captação de Dopamina/sangue , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Levodopa/uso terapêutico , Masculino , Fenilalanina/deficiência , Fenilalanina/metabolismo , Autoadministração , Fatores de Tempo , Tirosina/deficiência , Tirosina/metabolismo
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