Tyramine exerts hypolipidemic and anti-obesity effects in vivo

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine

Doxycycline at subantimicrobial dose combined with escitalopram reverses depressive-like behavior and neuroinflammatory hippocampal alterations in the lipopolysaccharide model of depression.

Doxycycline (DOXY) is a second-generation tetracycline with anti-inflammatory and neuroprotective effects. A proinflammatory profile seems to predict the severity of depressive symptoms. In the present study, we aimed at determining whether the anti-inflammatory action of subantimicrobial-dose doxycycline (SDD) (DOXY, 10mg/kg), alone or combined with the antidepressant escitalopram (ESC), could revert lipopolysaccharide-induced depressive-like alterations in mice. Male Swiss mice received saline or lipopolysaccharide (LPS) for ten consecutive days. From the 6th day of LPS exposure, they were treated with DOXY 10 mg/kg, ESC 4 mg/kg, DOXY 10 mg/kg plus ESC 4 mg/kg (DOXY+ESC), or saline. On the 10th day, we assessed behavioral despair (forced swimming test), anhedonia (sucrose preference test), brain oxidative stress markers, and inflammatory and protective pathways related to depression, such as NF-kB and phospho-CREB. Our results showed that DOXY alone or combined with ESC reduced hippocampal Iba-1 expression and interleukin (IL)-1ß levels. Only DOXY+ESC successfully reversed the LPS-induced increase in NF-kBp65 expression and TNFα levels. DOXY caused a marked increase in the hippocampal expression of phospho-CREB and GSH concentrations. DOXY and DOXY+ESC showed a tendency to modulate the functional status of mitogen-activated kinase p42-44 (Phospho-p44/42 MAPK) and of the phosphorylated form of glycogen synthase kinase 3 beta (GSK3ß), revealing a protective profile against inflammation. In conclusion, SDD, combined with ESC, seems to be a good strategy for reverting inflammatory changes and protecting against depression.

Effects of botulinum toxin type A for spastic foot in post-stroke patients enrolled in a rehabilitation program.

UNLABELLED: The objective of this study was to evaluate the effects of botulinum toxin type A (BTX-A) on spastic foot in stroke patients in a rehabilitation program. METHOD: Hemiparetic stroke patients (n=21) enrolled in a rehabilitation program were divided into two groups. The first group (n=11) received a total of 300 UI BTX-A, and the second group (n=10) received 100 UI BTX-A. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for Modified Ashworth Score, time walking 10 meters, and the Functional Independence Measure (mFIM) motor score. RESULTS: The higher-dose group exhibited a significant improvement in spasticity, and both groups showed an improvement in time walking 10 meters and mFIM, with no significant differences between them. CONCLUSIONS: Our findings suggest that gains in gait velocity and functional independence were not correlated to BTX-A dose.

Effects of botulinum toxin type A for spastic foot in post-stroke patients enrolled in a rehabilitation program / Efeitos da toxina botulinica tipo A no pe espastico em pacientes pos-acidente vascular encefalico inseridos em programa de reabilitacao

The objective of this study was to evaluate the effects of botulinum toxin type A (BTX-A) on spastic foot in stroke patients in a rehabilitation program. Method: Hemiparetic stroke patients (n=21) enrolled in a rehabilitation program were divided into two groups. The first group (n=11) received a total of 300UI BTX-A, and the second group (n=10) received 100 UI BTX-A. All patients were assessed at baseline and 2, 4, 8 and 12 weeks after injection for Modified Ashworth Score, time walking 10 meters, and the Functional Independence Measure (mFIM) motor score. Results: The higher-dose group exhibited a significant improvement in spasticity, and both groups showed an improvement in time walking 10 meters and mFIM, with no significant differences between them. Conclusions: Our findings suggest that gains in gait velocity and functional independence were not correlated to BTX-A dose. .

O objetivo deste estudo foi avaliar os efeitos da toxina botulínica tipo A (TXB-A) sobre a espasticidade de membro inferior em pacientes pós-AVE em reabilitação. Método: 21 pacientes hemiparéticos foram divididos em dois grupos que receberam doses de TXB-A de 300UI (Grupo 1) e 100UI (Grupo 2) e foram avaliados antes da injeção e 2, 4, 8 e 12 semanas após, quanto à escala de Ashworth modificada, tempo para andar 10 metros e escore motor da Medida de Independência Funcional (MIFm). Resultados: O grupo que utilizou dose mais alta teve melhora significativa da espasticidade. Ambos os grupos tiveram melhora do tempo para andar 10 metros e da MIFm sem diferença significativa entre eles. Conclusões: A melhora da velocidade de marcha e da independência funcional não foram correlacionadas com a dose de TXB-A na amostra analisada. .

(-)-α-Bisabolol-induced gastroprotection is associated with reduction in lipid peroxidation, superoxide dismutase activity and neutrophil migration.

This work examined the gastroprotection of (-)-α-bisabolol, an unsaturated optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants. (-)-α-Bisabolol has been described as a compound capable of reducing the gastric ulcer area in response to absolute ethanol. We evaluated the gastroprotection of (-)-α-bisabolol in ethanol-induced gastric lesions model through histopathological assessment, measurement of the membrane lipids peroxidation (MDA), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, catalase (CAT) activity and the nitrite amount. Our results showed that (-)-α-bisabolol was able to reduce injuries associated with the administration of ethanol and the formation of thiobarbituric acid reactive substances (MDA) was also able to increase SOD activity and reduce the influx of cells inflammatory (neutrophils) in the gastric mucosa. The effect of (-)-α-bisabolol seems to be unrelated to the nitric oxide. (-)-α-Bisabolol caused a reduction of catalase activity. These findings show that (-)-α-bisabolol is able to decrease oxidative stress and inflammatory event associated with the lesions induced by ethanol.

B vitamins attenuate haloperidol-induced orofacial dyskinesia in rats: possible involvement of antioxidant mechanisms.

Tardive dyskinesia (TD) is a serious motor disorder related to antipsychotic therapy, whose pathophysiology is associated to oxidative stress. Treatments that maintain antipsychotic efficacy while reducing TD risk are awaited. Haloperidol (HAL), a typical antipsychotic, is used as a putative murine model of TD. Here, we evaluated the protective role of vitamins B1, B6, and B12 alone or in combination (vitamin B cocktail) in preventing the HAL-induced orofacial dyskinesia (OD), based on their antioxidant properties. HAL (1 mg/kg) administered intraperitoneally to Wistar rats for 21 days caused OD and increased catalepsy time. The daily administration of B vitamins (B1 : B6 : B12 at 60 : 60 : 0.6 mg/kg) alone or the vitamin B cocktail, along with HAL, prevented the development of OD. Catalepsy time reduced in all groups treated with B vitamins, but to a lesser extent than OD. The participation of oxidative stress was assessed by the determination of reduced glutathione (GSH) levels and lipid peroxide formation in the striatum. HAL significantly decreased GSH levels and enhanced lipid peroxidation, whereas B1, B12, and vitamin B cocktail prevented the decrease in GSH levels. All groups treated with B vitamins presented a decrease in lipid peroxide formation. The data suggest a promising role for B vitamins in the prevention of OD.

The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson's disease: a review.

ABSTRACT This work reviews the evidence of the mechanism of neuronal degeneration in Parkinson's disease (PD) and the neuroprotective effect of lipoic acid and its use in the treatment of PD. PD is characterized by slow and progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, leading to reduction of the striatal dopaminergic terminals. It is known that several factors influence neuronal damage. Among these factors, oxidative stress, immune system activity, microglial cells, and apoptotic mechanisms are of major importance. Currently, several antioxidants have been studied with the aim of reducing/slowing the progression of neurodegenerative processes. Lipoic acid is considered a universal antioxidant because it is an amphipathic substance. Lipoic acid and its reduced form, dihidrolipoic acid, act against reactive oxygen species, reducing oxidative stress. Therefore, this antioxidant has been used in the treatment of many diseases, including a new perspective for the treatment of Parkinson's disease.

Melatonin: pharmacological aspects and clinical trends.

Melatonin, N-acetyl-5-methoxytryptamine, the major hormone produced by the pineal gland under the influence of the dark/light cycle, has been shown to have a large number of therapeutic possibilities. It has been utilized in several countries for circadian rhythm disorders, sleep disturbances, jet lag, and sleep-wake cycle disturbances in blind people, and shift workers. In our mechanism of act, the G(i) protein-coupled metabotropic melatonin receptors MT1 and MT2 are the primary mediators of the physiological actions of melatonin. This hormone plays an important role in the regulation of physiological and neuroendocrine functions, such as synchronization of seasonal reproductive rhythms and entrainment of circadian cycles. In addition to its chronobiological role, several pharmacological effects of melatonin have been reported in mammals including sedative, antioxidant, anxiolytic, antidepressant, anticonvulsant, and analgesic activities. There is some evidence from clinical trials that melatonin can be helpful in that event. Current trends of pharmacological functions of melatonin pointed out its use in the treatment of neurodegenerative and neoplastic diseases. These effects and uses of melatonin are mentioned but further confirmatory studies are needed in most of them.

Esquizofrenia: uma doença inflamatória?: [revisão] / Schizophrenia: an inflammatory disease?: [review]

OBJETIVO: Neste estudo, o objetivo foi revisar o papel de um possível processo inflamatório na gênese da esquizofrenia. MÉTODO: Foram selecionados os trabalhos publicados em revistas indexadas nas bases de dados Lilacs e MedLine, sob os unitermos "esquizofrenia", "inflamação" e "estresse oxidativo", nos últimos 10 anos até dezembro de 2009, nos idiomas inglês e português. Foram excluídos os artigos que tratavam de aspectos fisiopatológicos da doença fora do interesse da psiquiatria. RESULTADOS: Sessenta e um artigos foram selecionados. Doze abordavam o envolvimento do estresse oxidativo na esquizofrenia, nove tratavam de alterações no sistema imunológico de pacientes esquizofrênicos, dezesseis da infecção pré-natal como desencadeador da doença e sete mostravam a ação antioxidante e anti-inflamatória de fármacos antipsicóticos. CONCLUSÃO: Os estudos enfatizam o envolvimento do sistema imunológico (isto é, interleucinas e ação anti-inflamatória dos antipsicóticos), das infecções, do estresse oxidativo e da função mitocondrial na fisiopatologia da esquizofrenia. Portanto, esses novos achados são importantes para a melhor compreensão e, consequentemente, a elaboração de terapias mais específicas e eficazes no combate dessa doença mental.

OBJECTIVE: We aimed at reviewing about the influence of the inflammatory process in the genesis of schizophrenia. METHOD: A search for papers published in Lilacs and MedLine databases during the last 10 years until December 2009 was made using the terms "schizophrenia", "inflammation" and "oxidative stress". The papers concerning other pathophysiologic aspects of schizophrenia not exclusively related to psychiatry were excluded. RESULTS: Sixty-one articles were selected: twelve were involved the role of oxidative stress, nine dealt with changes in the immune system, and sixteen referred to prenatal infection as the trigger of schizophrenia. Seven articles showed the anti-inflammatory and antioxidant action of antipsychotic drugs. CONCLUSION: The studies emphasized the importance of the mitochondrial function, oxidative stress, immunological system (interleukin, anti-inflammatory action of the antipsychotics) and infections in the pathophysiology of schizophrenia. These findings are important for a better understanding and consequently the development of more specific and effective therapies for schizophrenia.

Reações adversas causadas por fármacos que atuam no sistema nervoso: análise de registros de um centro de farmacovigilância do Brasil / Adverse reaction caused by drugs acting in nervous system: records analysis of a farmacovigilance center in Brazil

CONTEXTO: A morbimortalidade por uso de medicamentos é um grande problema de saúde. As reações adversas a medicamentos podem resultar em óbito, aumento de internações hospitalares e dos custos com a saúde. OBJETIVOS: Descrever e analisar as notificações de suspeitas de reações adversas causadas por medicamentos que atuam no sistema nervoso (RAM-SN), registradas no Centro de Farmacovigilância do Ceará, de janeiro de 1997 a março de 2008. MÉTODOS: As RAM-SN foram classificadas segundo os critérios da Organização Mundial da Saúde. Uma relação de causalidade entre o fármaco administrado e a reação adversa identificada foi realizada, bem como a análise da reação quanto à gravidade. RESULTADOS: Foram registradas 176 notificações de RAM-SN. A maioria (n = 145; 82,4 por cento) ocorreu no ambiente hospitalar. O principal notificador foi o farmacêutico. As RAM-SN foram classificadas como: possíveis (n = 110), prováveis (n = 37) e definidas (n = 17). Quanto à gravidade, foram consideradas: leves (n = 21), moderadas (n = 127), graves (n = 15) e fatais (n = 1). O caso fatal foi notificado por médico e envolveu medicamentos anestésicos. Geralmente, as reações adversas observadas foram causadas predominantemente por analgésicos, anestésicos e antiepilépticos. DISCUSSÃO: Os dados demonstram o valor potencial de se ter acesso a sistemas de farmacovigilância local para registrar possíveis riscos com o uso de fármacos.

BACKGROUND: The morbi-mortality by the use of medicines is a major health problem. The drug adverse reactions may result in death, increased hospitalizations and healthcare costs. OBJECTIVES: Describe and analyze reports of suspected adverse reactions caused by drugs that act on the nervous system (SN-ADR), registered in the database of the Pharmacovigilance Centre of Ceará, from January 1997 to March 2008. METHODS: All the NS-ADRs were classified according to criteria of the World Health Organization. The causality between the drug administered and the adverse reaction was established, as well as the analysis regarding to the severity of the reaction. RESULTS: The Centre recorded 176 notifications of RAM-SN. The most of the reactions occurred in the hospital. The main reporter was the pharmacist. All the RAM-SN were classified as possible (n = 110), probable (n = 37) and definite (n = 17). With regard to severity, the NS-ADRs were considered: light (n = 21), moderate (n = 127), serious (n = 15) and fatal (n = 1). The fatal case was reported by physician, and involved anesthetic drugs. In general the adverse reactions observed were caused predominantly by analgesics, anesthetics and antiepileptics. DISCUSSION: The data demonstrate the potential values of accessing to a local system of pharmacovigilance to report possible risks with the use of nervous system drugs.

Determination of amino acid levels in the rat striatum, after administration of ethanol alone and associated with ketamine, a glutamatergic antagonist.

The main goal of this study was to determine the amino acids (glutamate, aspartate, glutamine and tyrosine) levels in the rat striatum, after ethanol administration alone and/or associated with ketamine. In protocol 1 (Et+ketamine-1), ethanol was administered to male Wistar rats until the 7th day, and at the next day the group received only ketamine (25mg/kg, i.p.) up to the 14th day. In protocol 2 (Et+ketamine-2), ethanol was also administered up to the 7th day, and was associated with ketamine from the 8th up to the 14th day. In other groups, animals were treated daily with ethanol (4 g/kg, p.o.), for 7 or 14 days or ketamine daily for 7 days. Controls were administered with distilled water for 7 days. Results showed that, in protocol 1, aspartate (ASP) levels increased after ketamine administration, as compared to the controls. This effect was inhibited in the group Et+ketamine-1. Ethanol (7 days) increased glutamate (GLU) levels, as compared to control, and this effect did not differ significantly from that observed in the ketamine group. When ketamine was administered after the ethanol withdrawal (protocol 1), no alterations in those amino acid concentrations were seen, as compared to the control and ketamine groups. A tendency for increasing GLU levels was observed, after administration of ethanol (14 days) or ketamine alone or associated (protocol 2), when compared to control values. In protocol 2, TYR levels decreased as related to controls and to the 14-day ethanol-treated group. We can assume that ketamine presents only an antagonist effect, in animals pretreated with ethanol, followed by ketamine administered from the 8th day on. This is due to the fact that NMDA receptors are already sensitized, leading to a decrease in these receptors functions and consequently to ASP and GLU releases.

Êxtase (MDMA): efeitos farmacológicos e tóxicos, mecanismo de ação e abordagem clínica / Ecstasy (MDMA): pharmacological and toxic effects, mechanism of action and clinical management

CONTEXTO: O 3,4-metilenodioximetanfetamina (MDMA, êxtase) é um derivado da anfetamina, cujo consumo por jovens tem aumentado. OBJETIVOS: Conduzir uma revisão de literatura sobre os aspectos farmacológicos e fisiopatológicos do MDMA, incluindo o mecanismo de ação que possa explicar os efeitos neurotóxicos e a toxicidade aguda e a longo prazo. MÉTODOS: Revisão da literatura usando as palavras-chave: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, drug abuse, por intermédio do MEDLINE e LILACS. A busca incluiu todos os artigos publicados no período entre 1985 e 2007. RESULTADOS: Ainda existem muitas questões sem respostas sobre a farmacologia do êxtase e a fisiopatologia dos efeitos tóxicos dessa substância. A simples descrição do mecanismo de ação é insuficiente para explicar todos os efeitos induzidos pelo êxtase. O mecanismo exato responsável por mediar os efeitos tóxicos do MDMA sobre os neurônios da serotonina precisa ser elucidado. CONCLUSÕES: Existem poucas informações na literatura sobre a farmacologia e o mecanismo de ação do MDMA que possam explicar os efeitos neurotóxicos e outros efeitos fisiopatológicos. São necessários mais estudos para que o profissional de saúde possa obter informações e conhecimentos a fim de combater os efeitos terríveis do êxtase na população jovem vulnerável.

BACKGROUND: The consumption of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by young people increased in the past years. OBJECTIVES: To conduct a literature review on the pharmacology of MDMA and particularly with respect to the putative mechanism of action implicated in the acute and long-term toxicity and neurotoxic effects. METHODS: A literature review using the key words: 3,4-methylenedioxymethamphetamine, ecstasy, neurotoxicity, intoxication, abuse drugs was performed in the databases MEDLINE and LILACS. The search covered all articles published between 1985 and 2007. RESULTS: There were still many unanswered questions regarding the pharmacology of ecstasy and the pathophysiology of its toxic effects. The fundamental mechanism of action is insufficient to explain all effects induced by the drug. The exact mechanism responsible for mediating the toxic effects of MDMA on 5-HT neurons remain to be elucidated. DISCUSSION: There is limited information in published literature about the underlying pharmacology and mechanism of action that could account for the neurotoxic and other phathophysiological effect of MDMA.

Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina / Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus

Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsöes e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.). Controles receberam salina. A concentraçäo dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observaçäo de 1 e 24h desencadearam estado epiléptico e näo sobreviveram à fase aguda do quadro convulsivo. Foi observada reduçäo nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativaçäo do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo

[Buspirone increases D2-like dopaminergic receptor density in rat corpus striatum]. / Buspirona aumenta a densidade de receptores dopaminérgicos D2- símile em corpo estriado de rato.

Buspirone (busp) a piperazinyl derivative with anxiolytic properties is a partial agonist on 5-HT1A with affinity for D2-like dopaminergic receptors (RD2). The objective of this study was to verify the effects of busp on RD2. Female Wistar rats 150-200 g were treated with busp (5 and 10 mg/kg, p.o.) 1 or 2 times daily for 7 days. Controls (C) received saline. The density of RD2 (fmol/mg protein) was determined through binding assays in striatum (ST) using [3H]-spiroperidol as radioligand. No alteration in Bmax or Kd values were seen after busp administration once a day. However, a RD2 upregulation of 55 % increase was observed after busp 2 times a day with no change in Kd values. The results showed that busp interact not only with serotonergic, but also with dopaminergic system.

Buspirona aumenta a densidade de receptores dopaminérgicos D2- símile em corpo estriado de rato / Buspirone increases D2-like dopaminergic receptor density in rat corpus striatum

Buspirona (busp) é um derivado piperazinil com propriedades ansiolíticas que atua como agonista parcial nos receptores serotonérgicos (5-HT1A) e que tem afinidade por receptores dopaminérgicos D2-símile (RD2). O objetivo desse estudo foi verificar os efeitos da busp nos RD2 em corpo estriado de ratos. Ratas Wistar, fêmeas (150-200 g) foram tratadas com busp (5 e 10 mg/kg, v.o.) 1 ou 2 vezes por dia durante 7 dias. Controles receberam salina. A densidade dos receptores D2 foi determinada através de ensaios de binding em CE de rato usando [³H]-espiroperidol como radioligante. Nenhuma alteraçäo nos valores de Bmax e Kd foi observada depois da administraçäo de buspirona uma vez ao dia. Contudo, foi verificado aumento de 55 por cento na densidade dos receptores D2 após a administraçäo de buspirona 2 vezes por dia sem nenhuma alteraçäo nos valores de Kd. Os resultados mostraram que a busp interage näo somente com o sistema serotonérgico mas também com o sistema dopaminérgico

Interação dopamina-acetilcolina: ação de drogas que atuam nos sistemas dopaminérgico e colinérgico em cortex motor e corpo estriado de rato / Interaction acetylcholine, dopamine: drug action acting on cholinergic and dopaminergic systems in motor cortex and striatum of mouse

Neste trabalho foram estudadas as interações entre os sistemas dopaminérgico e colinérgico em córtex motor e corpo estriado de rato. As seguintes drogas foram utilizadas: mazindol e cocaína (agonistas dopaminérgicos indiretos), apomorfina (agonista dopaminérgico D1/D2 símile), pimozida e sulpirida (antagonistas D2-símile), carbacol (agonista muscarínico M2-símile) e atropina (antagonista muscarínico M1/M2-símile). As interações foram investigadas em alguns parâmetros: densidade de receptores muscarínicos (M1+M2-símile, M1 e M2-símile) e dopaminérgicos (D1 e D2-símile); níveis de nucleotídeos cíclicos (AMPc e GMPc); atividade da acetilcolinesterase; e comportamento (campo aberto e catalepsia). Os resultados mostraram que existem alterações não somente em corpo estriado, como também em córtex motor de ratos. Em córtex motor, o mazindol e a apomorfina aumentaram a densidade de receptores muscarínicos, preferencialmente sobre os receptores M1-símile. O aumento na densidade de receptores induzido por estas drogas foi bloqueado pela pimozida. Em corpo estriado, de modo similar ao que ocorreu em córtex motor, agonistas dopaminérgicos (mazindol e apomorfina e incluindo também cocaína) aumentaram a densidade de receptores muscarínicos. Do mesmo modo, o carbacol e a atropina aumentaram a densidade de receptores dopaminérgicos, preferencialmente D1-símile. A associação de pimozida e carbacol causou aumento significativo dos níveis de AMPc em corpo estriado, alteração esta não observada quando as drogas foram administradas isoladamente. Em córtex motor, a atropina diminuiu os níveis de AMPc, efeito que não foi observado com esta droga na presença do mazindol. O mazindol diminuiu a atividade da acetilcolinesterase em corpo estriado, efeito este bloqueado pelo pimozida que sozinha não apresentou efeito significativo. Além disto, o mazindol aumentou a atividade locomotora e quando associado a atropina este efeito foi potencializado...