RESUMO
Ketamine is an anesthetic derivative of phencyclidine (PCP; 'Angel dust') with dissociative, analgesic and psychedelic properties. Ketamine has become a popular recreational drug of abuse in many parts of the world in recent years. The preclinical studies demonstrate the reinforcing effects of ketamine and long-term ketamine abuse induces a delayed and persistent upregulation of dopamine system. In humans, there have been concerns about its liability to development of addiction. The dilemma of mental professionals in managing the treatment-seeking ketamine abusers comes from a lack of effective pharmacotherapy. Limiting evidence showed that lamotrigine, which inhibits glutamate release, is effective to reduce cocaine craving. We propose that lamotrigine might be beneficial for managing ketamine use disorder clinically. We also reported one case of ketamine use disorder who experienced a great reduction in craving and ketamine use after taking lamotrigine. Although the mechanisms underlying neuroadaptation and reward related to ketamine are not entirely clear, future clinical trials are needed to advance our understanding of the benefit yielded by lamotrigine to treat ketamine use disorder.
Assuntos
Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina , Abuso de Fenciclidina/tratamento farmacológico , Triazinas/uso terapêutico , Adulto , Animais , Humanos , Ketamina/administração & dosagem , Ketamina/toxicidade , Lamotrigina , Masculino , Modelos Biológicos , Abuso de Fenciclidina/fisiopatologia , Abuso de Fenciclidina/psicologiaRESUMO
Accumulating evidence suggests that dysregulation of histone modification is involved in the pathogenesis and/or pathophysiology of psychiatric disorders. However, the abnormalities in histone modification in the animal model of schizophrenia and the efficacy of antipsychotics for such abnormalities remain unclear. Here, we investigated the involvement of histone modification in phencyclidine-induced behavioral abnormalities and the effects of antipsychotics on these abnormalities. After repeated phencyclidine (10 mg/kg) treatment for 14 consecutive days, mice were treated with antipsychotics (clozapine or haloperidol) or the histone deacetylase inhibitor sodium butyrate for 7 d. Repeated phencyclidine treatments induced memory impairment and social deficit in the mice. The acetylation of histone H3 at lysine 9 residues decreased in the prefrontal cortex with phencyclidine treatment, whereas the expression level of histone deacetylase 5 increased. In addition, the phosphorylation of Ca²âº/calmodulin-dependent protein kinase II in the nucleus decreased in the prefrontal cortex of phencyclidine-treated mice. These behavioral and epigenetic changes in phencyclidine-treated mice were attenuated by clozapine and sodium butyrate but not by haloperidol. The dopamine D1 receptor antagonist SCH-23390 blocked the ameliorating effects of clozapine but not of sodium butyrate. Furthermore, clozapine and sodium butyrate attenuated the decrease in expression level of GABAergic system-related genes in the prefrontal cortex of phencyclidine-treated mice. These findings suggest that the antipsychotic effect of clozapine develops, at least in part, through epigenetic modification by activation of the dopamine D1 receptor in the prefrontal cortex.
Assuntos
Antipsicóticos/farmacologia , Clozapina/farmacologia , Epigênese Genética/efeitos dos fármacos , Abuso de Fenciclidina/tratamento farmacológico , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de Dopamina D1/metabolismo , Animais , Benzazepinas/farmacologia , Ácido Butírico/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Antagonistas de Dopamina/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Alucinógenos/farmacologia , Haloperidol/farmacologia , Antagonistas dos Receptores Histamínicos/farmacologia , Histona Desacetilases/metabolismo , Histonas/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Endogâmicos ICR , Fenciclidina/farmacologia , Abuso de Fenciclidina/complicações , Abuso de Fenciclidina/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Dopamina D1/antagonistas & inibidoresAssuntos
Encéfalo/efeitos dos fármacos , Drogas Ilícitas , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacologia , Encéfalo/metabolismo , Cannabis/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/farmacologia , Atenção à Saúde/organização & administração , Dopamina/metabolismo , Política de Saúde/legislação & jurisprudência , Humanos , Entorpecentes/efeitos adversos , Entorpecentes/farmacologia , Nicotina/efeitos adversos , Nicotina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Abuso de Fenciclidina/diagnóstico , Abuso de Fenciclidina/tratamento farmacológico , Abuso de Fenciclidina/etiologia , Abuso de Fenciclidina/psicologia , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
Phencyclidine has a wide range of deleterious effects. Drug users may not even know that they have taken PCP since it is so easily disguised. Physicians should look for decreased reality testing, erythema, dry skin and other manifestations. The varied signs and symptoms of acute intoxication can be dealt with quickly and effectively. Management strategies include acidification of the urine and diuresis, as well as more specific antidotes, depending on the neurotransmitter system most affected.
Assuntos
Abuso de Fenciclidina/tratamento farmacológico , Humanos , Abuso de Fenciclidina/diagnóstico , Abuso de Fenciclidina/terapiaRESUMO
A previously healthy 33-year-old patient developed a schizophrenia-like psychosis of 5 weeks' duration after inhalation of hashish contaminated with phencyclidine (PCP). The literature is reviewed and the epidemiology, clinical features, therapy and neuropharmacology of phencyclidine intoxication are discussed.
Assuntos
Cannabis , Abuso de Fenciclidina/complicações , Psicoses Induzidas por Substâncias/etiologia , Adulto , Fenômenos Químicos , Química , Humanos , Masculino , Metotrimeprazina/uso terapêutico , Fenciclidina/metabolismo , Abuso de Fenciclidina/tratamento farmacológico , Abuso de Fenciclidina/fisiopatologia , Psicoses Induzidas por Substâncias/tratamento farmacológicoRESUMO
Rats trained to discriminate between phencyclidine and saline vehicle were used to test various agents for their ability to mimic or block the phencyclidine cue. ketamine, dexoxadrol, tiletamine, and phencyclidine analogs were found to mimic phencyclidine's behavioral effects. Treatment with the adenosime receptor agonists N6-cyclohexyladenosine and L-phenylisopropyladenosine blocked the discriminative properties of phencyclidine. These results suggest that adenosine receptor agonists might be useful in treating phencyclidine-induced psychosis.
Assuntos
Fenciclidina/farmacologia , Receptores de Superfície Celular/efeitos dos fármacos , Adenosina/análogos & derivados , Animais , Dioxolanos/farmacologia , Humanos , Ketamina/farmacologia , Abuso de Fenciclidina/tratamento farmacológico , Piperidinas/farmacologia , Ratos , Receptores Purinérgicos , Tiletamina/farmacologiaRESUMO
Twenty-four patients with phencyclidine intoxication were treated with either physostigmine (2 mg i.m.) or haloperidol (5 mg i.m.) based on the presence of delusions and/or hallucinations. Several symptoms subsequently improved. Schizophreniform symptoms showed substantial improvement with haloperidol.