Poisoning in domestic cats in Brazil: toxicants, clinical signs, and therapeutic approaches / [Intoxicação em gatos domésticos no Brasil: toxicantes, sinais clínicos e abordagens terapêuticas]

This study evaluated the most common toxic agents affecting domestic cats, the clinical signs of toxicity, and the therapeutic approaches for recovery. A survey on poisoning in cats was conducted among small animal veterinary practitioners from 2017 to 2018. Of the 748 completed questionnaires, 543 (72.6%) were evaluated. Pesticides and household cleaning supplies were the most common causes of poisoning in cats. The toxicant groups included pesticides and household cleaning supplies (organophosphates), human drugs (acetaminophen), plants/plant derivatives (lily), and veterinary drugs (tramadol). The major clinical signs for these four groups of toxicants were (1) acetaminophen poisoning, which caused oxidative erythrocyte damage; (2) muscarinic and nicotinic cholinergic syndrome, which resulted from organophosphate poisoning; (3) acute kidney injury, which resulted from intoxication of lily; and (4) serotonin syndrome, which resulted from tramadol toxicosis. Interventions for treating poisoning in cats were based on the clinical presentation of animals. In the present study, the significant toxins identified to be dangerous for cats were characterized using the obtained data in Brazil as well as the main associated clinical signs and therapy recommended by veterinarians.(AU)

Objetiva-se com este trabalho caracterizar os principais toxicantes para gatos domésticos, bem como os prevalentes sinais clínicos e a terapêutica associada. Uma pesquisa sobre envenenamento em gatos foi realizada entre médicos veterinários no período de 2017 a 2018. Dos 748 questionários preenchidos, 543 (72,6%) foram avaliados. Pesticidas e domissanitários foram os principais causadores de intoxicação em gatos. Entre os grupos tóxicos, destacaram-se, na categoria pesticidas e domissanitários (organofosforados), medicamentos humanos (acetaminofeno), plantas e derivados de planta (lírio) e medicamentos veterinários (tramadol). Os principais sinais clínicos para os quatro grupos de substâncias tóxicas foram: (1) intoxicação por acetaminofeno, que causou dano eritrocitário oxidativo; (2) síndrome colinérgica muscarínica e nicotínica, resultante do envenenamento por organofosforado; (3) lesão renal aguda, causada pela intoxicação por lírio; e (4) síndrome serotoninérgica, resultante da exposição ao tramadol. As intervenções realizadas para o tratamento dos envenenamentos foram justificáveis mediante a apresentação clínica dos animais. Por meio dos dados obtidos, puderam-se caracterizar os principais tóxicos para gatos no Brasil, bem como os principais sinais clínicos associados e a terapêutica preconizada pelos médicos veterinários.(AU)

Serotonergic-like profile of 4-propyl-2hbenzo[h]-chromen-2-one (FCS-304) in mice and rats / Perfil de tipo serotoninérgico de 4-propil-2h-benzo[h]-cromen-2-ona (FCS-304) en ratones y ratas

Background: 4-propil-2H-benzo[h]-cromen-2-ona (FCS-304) is a semisynthetic coumarin with MAO-A inhibitory activity and positive results in forced swimming and tail suspension test in mice, but until now, it has not been studied in other screening antidepressant models in mice and rats. Objectives: The aim of this work was to assess the serotonin like effect of FCS-304 in the 5-hydroxytryptophan (5-HTP) test in mice, in the behavioral despair test in rats, and in the reserpine test in rats. Methods: Potentiation of 5-HTP (100 mg/kg, i.p.), induced head twitches were assessed in mice, previously treated with FCS-304 (50-75-150 mg/kg, p.o.). The behavioral despair test was performed in rats treated with FCS-304, recording the immobility time attained by the animals subjected to forced swimming. Antagonism of reserpine-induced ptosis was examined in rats, assessing the level of palpebral closure. Imipramine (30 mg/kg, p.o.) and vehicle (canola oil) served as positive and negative controls, respectively. Results: FCS-304 significantly potentiated 5-HTP induced head twitches in mice, in a dose dependent manner. In rats, FCS-304 significantly decreased the immobility time in the behavioral despair test and antagonized reserpine induced ptosis. Conclusions: These results add support to propose that FCS-304 could elicit antidepressant effects related to MAO-A inhibitory activity.

Antecedentes: 4-propil-2H-benzo[h]-cromen-2-ona (FCS-304) es una cumarina semisintética inhibidora de MAO-A con efectos positivos en las pruebas de nado forzado y suspensión por la cola en ratones, sin embargo, hasta ahora no se había estudiado en otros modelos de tamizado antidepresivo en ratones y ratas. Objetivos: el objetivo de este trabajo fue evaluar el efecto de tipo serotoninérgico de FCS-304 en la prueba de potenciación de 5-hidroxitriptofano (5-HTP) en ratones, y su respuesta en la prueba de desesperanza conductual en ratas y en la prueba de reserpina en ratas. Métodos: se evaluó la potenciación de las sacudidas de cabeza inducidas por 5-HTP (100 mg/kg, i.p.), en ratones tratados con FCS-304 (50-75-150 mg/Kg, v.o.). La prueba de desesperanza conductual se realizó en ratas tratadas con FCS-304, expuestas a nado forzado. El antagonismo de la ptosis palpebral inducida por reserpina se examinó en ratas determinando el grado de apertura ocular. Imipramina (30 mg/kg, v.o.) y el vehículo (aceite de canola, 0,1 mL/10 g), sirvieron como controles positivo y negativo, respectivamente. Resultados: FCS-304 incrementó significativamente el recuento de sacudidas de cabeza inducidas por 5-HTP en ratones, en función de la dosis. En ratas, FCS-304 fue efectiva para disminuir el tiempo de inmovilidad en la prueba de desesperanza inducida por nado forzado y el grado de ptosis palpebral inducido por reserpina. Conclusiones: estos resultados dan soporte para proponer que FCS-304 ejercería efectos de tipo antidepresivo relacionados con la inhibición de MAO-A.

Síndrome serotoninérgico / Serotonin syndrome

Introducción: el síndrome serotoninérgico es una rara afección, con reacción adversa a la administración de determinado grupo farmacológico. Objetivo: demostrar la evolución clínico-anestesiológica de un paciente con síndrome serotoninérgico. Caso clínico: paciente de 37 años con antecedentes de epilepsia, tratado con valproato de sodio. Ingresó al hospital por quemaduras de segundo y tercer grado en ambos miembros inferiores para debridamiento e implante de piel. Lleva tratamiento con tramadol 50 mg/6 h, ácido fólico 5 mg/d, fluoxetina 20 mg/d, tiamina 100 mg/d y vitamina C 500 mg/d. Se administró anestesia general con máscara laríngea. Inducción con fentanilo 100 µg, ketamina 20 mg, propofol 150 mg. Se colocó máscara laríngea 4. Respiración espontánea en modalidad PSVPro con O2 + aire + sevoflurane (CAM 0,6 por ciento). Cuando comenzó la asepsia quirúrgica se evidenció clonus en ambos miembros inferiores. No cambios hemodinámicos, ni de la temperatura (36,1 °C). Gasometría: alcalosis metabólica. Ionograma normal. Se administró 5 mg de midazolam. En el posoperatorio se retiró la máscara laríngea. TA: 106/60. Pulso: 95 lat/min. Temperatura: 35,8 °C, Sat Hb: 98 por ciento. Se constató clonus sostenido inducible al estímulo mínimo bilateral, clonus orbital e hiperreflexia. Se mantuvo en la sala de recuperación por dos horas. Se dio alta para la sala de cuidados especiales con indicaciones. Conclusiones: la evolución fue satisfactoria. Ante un paciente que llega de urgencia, se recomienda evaluar las enfermedades coexistentes y su tratamiento; no hacerlo puede traer consecuencias fatales(AU)

Introduction: The serotonin syndrome is a rare condition and includes an adverse reaction to the administration of a certain pharmacological group. Objective: To show the clinical-anesthesiological evolution of a patient with serotonin syndrome. Clinical case: A 37-year-old patient with a history of epilepsy, treated with sodium valproate. The patient was admitted to the hospital for second and third degree burns on both lower limbs for debridement and skin implant. The patient was treated with tramadol (50 mg every 6 hours), folic acid (5 mg every d), fluoxetine (20 mg every day), thiamin (100 mg every day), and vitamin C (500 mg every day). General anesthesia with laryngeal mask was administered. Induction with fentanyl (100 µg), ketamine (20 mg), propofol (150 mg). Laryngeal mask number 4 was placed. Spontaneous respiration in PSVPro modality with O2, air and sevoflurane (CAM 0.6 percent). When the surgical asepsis began, clonus was evident in both lower limbs. No hemodynamic or temperature changes (36.1 °C). Gasometry: metabolic alkalosis. Normal Ionogram. 5 mg of midazolam were administered. In the postoperative period, the laryngeal mask was removed. TA: 106/60. Pulse: 95 beats/min. Temperature: 35.8 °C, sat Hb: 98 percent. Sustained clonus inducible to minimal bilateral stimulus, orbital clonus and hyperreflexia was found. The patient remained in the recovery room for two hours and was released for the special care room with instructions. Conclusions: The evolution was satisfactory. When a patient arrives urgently, it is recommended to assess the coexisting diseases and their treatment; not doing so can bring fatal consequences(AU)

Terminalia arjuna bark extract attenuates picrotoxin-induced behavioral changes by activation of serotonergic, dopaminergic, GABAergic and antioxidant systems / 中国天然药物

Stress and emotion are associated with several illnesses from headaches to heart diseases and immune deficiencies to central nervous system. Terminalia arjuna has been referred as traditional Indian medicine for several ailments. The present study aimed to elucidate the effect of T. arjuna bark extract (TA) against picrotoxin-induced anxiety. Forty two male Balb/c mice were randomly divided into six experimental groups (n = 7): control, diazepam (1.5 mg·kg), picrotoxin (1 mg·kg) and three TA treatemt groups (25, 50, and 100 mg/kg). Behavioral paradigms and PCR studies were performed to determine the effect of TA against picrotoxin-induced anxiety. The results showed that TA supplementation increased locomotion towards open arm (EPM) and illuminated area (light-dark box test), and increased rearing frequency (open field test) in a dose dependent manner, compared to picrotoxin (P < 0.05). Furthermore, TA increased number of licks and shocks in Vogel's conflict. PCR studies showed an up-regulation of several genes, such as BDNF, IP, DL, CREB, GABA, SOD, GPx, and GR in TA administered groups. In conclusion, alcoholic extract of TA bark showed protective activity against picrotoxin in mice by modulation of genes related to synaptic plasticity, neurotransmitters, and antioxidant enzymes.

Serotonin Syndrome after Clomipramine Overdose in a Child

Serotonin syndrome (SS) is a potentially life-threatening condition associated with increased serotonergic activity in central nervous system and may occur during the use of serotonergic drugs. Although increasing frequency of serotonergic drug use in children, pediatricians, emergency medicine and pediatric intensive care specialists have not enough knowledge and experience about SS that is a potentially life-threatening condition. A 12-year-old girl patient was admitted to our emergency room with the history of involuntary contractions on her extremities and alteration of consciousness. Her physical examination showed agitation, hyperthermia, dilated pupils, tremor, increased deep tendon reflexes, positive spontaneous clonus, agitation, flushed skin and diaphoresis, excessive perspiration, and continuous horizontal ocular movements. The patient diagnosed as SS by clinical history, physical and laboratory findings. In this paper, we will discuss SS occurred in a 12-year-old girl after concurrent clomipramine and risperidone use.

A Case of Postpartum Reversible Cerebral Vasoconstriction Syndrome / 대한내과학회지

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by development of a severe thunderclap headache with or without other acute neurological symptoms, and by multifocal or diffuse segmental vasoconstriction of the cerebral arteries that resolves spontaneously within 3 months. Several precipitating factors have been identified; these include the use of adrenergic or serotonergic drugs and postpartum status. Diagnosis is aided by the dynamic nature of the clinicoradiological features, including a 'beads-on-a-string' appearance of the cerebral arteries on angiography, and complete (or near-complete) resolution of the condition evident on repeat angiography performed 3 months after initial onset. Calcium channel blockers such as nimodipine seem to relieve the severe headache within 48 h. Here, we present the case of a female who developed RCVS postpartum.

Chronotype in Relation to Bipolarity, Suicidal Ideation, and Auditory Evoked Potentials in Patients with Major Depressive Disorder : Preliminary Study

OBJECTIVES: The current study investigated the putative relationship between chronotype and suicidality or bipolarity in patients with major depressive disorder (MDD). METHOD: Nineteen outpatients who met the criteria for MDD according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders-text revision were recruited for the current study. The subjects were divided into two subgroups based on their Basic Language Morningness (BALM) scores (dichotomized according to the median BALM score). The Loudness Dependence of Auditory Evoked Potentials (LDAEP) was evaluated by measuring the auditory event-related potentials before beginning medication with serotonergic agents. In addition, K-Mood Disorder Questionaire (K-MDQ), Beck Scale for Suicidal Ideation (BSS), Beck Hopelessness Scale (BHS), Barratt Impulsiveness Scale (BIS) were applied. RESULTS: The K-MDQ, BSS, BHS, BIS score was higher for the eveningness group than for the morningness group. However, the LDAEP, Hamilton Depression Rating Scale, Hamilton Anxiety Scale scores did not differ significantly between them. There were negative correlations between the total BALM score and the total K-MDQ, BSS, and BHS scores (r = -0.64 and p = 0.0033, r = -0.61 and p = 0.0055, and r = -0.72 and p = 0.00056, respectively). CONCLUSIONS: Depressed patients with eveningness are more vulnerable to the suicidality than those with morningness. Eveningness is also associated with bipolarity.

Drug interactions and possible serotonin syndrome in a patient with fibromyalgia / Interacciones medicamentosas y posible síndrome serotoninérgico en un paciente con fibromialgia

La depresión asociada con la fibromialgia puede tratarse con inhibidores selectivos de la recaptación de serotonina (ISRS) como fluoxetina, paroxetina o citalopram; o con inhibidores de la recaptación de serotonina y norepinefrina (duloxetina o milnacipran). En los pacientes con fibromialgia, varios metanálisis han demostrado la efectividad de los antidepresivos, en particular la amitriptilina, el antidepresivo tricíclico (TCA), que reduce el dolor, la fatiga, la depresión y los trastornos del sueño. Además, el tramadol, la pregabalina y la gabapentina son otras opciones de tratamiento.

Neurotoxicidade de pesticidas organofosforados durante o desenvolvimento: alterações bioquímicas e comportamentais / Neurotoxicity of organophosphorus pesticides during development: behavioral and biochemical changes

Pesticidas organofosforados são amplamente usados e seu uso constitui um grave problema de saúde pública. A ação clássica destes compostos é a inibição irreversível da acetilcolinesterase, promovendo acúmulo de acetilcolina nas sinapses e hiperestimulação colinérgica. No entanto, as consequências da exposição a baixas doses podem se estender a outros mecanismos de ação e sistemas neurotransmissores. Considerando que crianças constituem um grupo particularmente vulnerável aos efeitos de pesticidas, neste trabalho investigamos os efeitos da exposição aos organofosforados metamidofós (MET) e clorpirifós (CPF) durante o desenvolvimento sobre os sistemas colinérgico e serotoninérgico e sobre o comportamento de camundongos. Para isso, camundongos suíços foram expostos a injeções subcutâneas de MET, clorpirifós ou veículo do terceiro (PN3) ao nono (PN9) dias de vida pós-natal. As doses de exposição foram previamente escolhidas através da construção de uma curva dose-resposta que identificou como mais adequadas para este estudo as doses de 1mg/kg de MET e 3mg/kg de CPF, as quais promoveram em torno de 20% de inibição da acetilcolinesterase. Em PN10, parte dos animais foi sacrificada e foram avaliados os sistemas colinérgico e serotoninérgico no tronco encefálico e córtex cerebral. De PN60 a PN63, os animais foram submetidos a uma bateria de testes comportamentais. Em seguida, estes animais também foram sacrificados tendo sido avaliados os sistemas colinérgico e serotoninérgico. Em PN10, MET e CPF causaram alterações que sugerem aumento da atividade colinérgica respectivamente no tronco e córtex em fêmeas. No sistema serotoninérgico, apenas CPF promoveu alterações, aumentando a ligação ao receptor 5HT1A e transportador 5HT em fêmeas e diminuindo na ligação ao 5HT2. Em PN63, a atividade da acetilcolinesterase foi reestabelecida em todos os grupos. Ainda assim, MET diminuiu a atividade da colina acetiltransferase no córtex e a ligação ao transportador colinérgico.

Organophosphate pesticides are widely used and its use consist on a severe public health problem. The classic effect of these compounds involve irreversible inhibition of the enzyme acetylcholinesterase, causing an accumulation of acetylcholine at cholinergic synapses and, consequently, cholinergic hyperstimulation. However, when the doses of exposure are low, other the mechanisms of action may play a role and other neurotransmitter systems may be affected. Considering that children are particularly vulnerable to effects of these compounds, in this study we investigated the effects of methamidophos and chlorpyrifos organophosphate exposure during development on cholinergic and serotonergic systems and behavior. For this purpose, Swiss mice received subcutaneous injections of methamidophos or chlorpyrifos, or vehicle from the third to the nineth postnatal day (PN3 - PN9). Initially, a dose-response study was performed and the doses of 1mg/kg methamidophos and 3mg/kg chlorphrifos, which promoted 20% inhibition of acetylcholinesterase activity in brain were chosen to be used in the next set of experiments. At PN10, one day after exposure, a group of animals was sacrificed and the brainstem and cortex collected and stored to further analysis of cholinergic and serotonergic systems. From PN60 to PN63 the animals were submitted to behavioral tests in order to evaluate: anxiety, locomotor activity, decision making, depressive-like behavior and learning/memory. After the last test, the animals were sacrificed and the brainstem and cortex collected and stored to further analysis of cholinergic and serotonergic systems. At PN10, methamidophos and chlorpyrifos promoted alterations that suggest an increase of cholinergic activity respectively on the brainstem and cortex of females. As for the serotonergic system: only chlorpyrifos elicited alterations: There were increases in 5HT1A receptor and 5HT transporter binding in females and a decrease in 5HT2 receptor binding.

Serotonin Syndrome After an Overdose of Dextromethorphan and Chlorpeniramine: Two Case Reports

Dextromethorphan and chlorpeniramine are common ingredients of over-the-counter (OTC) cough pills. They are known to be safe when used alone, however, combination with other serotonergic drugs or use of an overdose can cause serotonergic toxicity. We report on a 43-year-old male and a 57-year-old female who ingested an overdose of antitussive drugs containing dextromethorphan and chlorpeniramine. They commonly presented with altered mentality and hyperreflexia on both upper and lower extremities. After conservative therapies, they were discharged with alert mentality. These cases are meaningful in that there are few cases of serotonin syndrome with an overdose of a combination of dextromethorphan and chlorpeniramine. Careful use with medication counseling for OTC cough pills is needed in order to prevent overdose of these ingredients.

Antidepressant-Like Effects of Lycii Radicis Cortex and Betaine in the Forced Swimming Test in Rats

The purpose of the present study was to examine the effect of Lycii Radicis Cortex (LRC) and betaine (BT) on immobility and neurochemical change in the forced swimming test (FST) in the rat. LRC, BT or fluoxentine was administered intraperitoneally to Sprague-Dawley rats three times (1, 5 and 23.5 h) before the FST. To investigate antidepressant-like effect, serotonin (5-HT) and norepinephrine (NE) were examined in the hippocampus and hypothalamus of rats. LRC (100 mg/kg) and BT (30, 100 mg/kg) significantly decreased the immobility time in the FST. LRC (100 mg/kg) significantly increased both 5-HT and NE levels in the hypothalamus of rats exposed to FST. BT (100 mg/kg) significantly increased 5-HT levels in the hypothalamus and hippocampus of rats. Taken together, these results demonstrated that improvement in the behavioral changes after LRC and BT administration may be mediated by elevation of 5-HT level in the hypothalamus and hippocampus, indicating a possible antidepressant-like activity. The present results suggest that the efficacy of LRC and BT in an animal model of depression may provide anti-depressant effects in human, which remains to be determined.

A Case of Serotonin Syndrome Induced by Fluoxetine and Duloxetine Independently in a Same Patient / 대한정신약물학회지

Here we report a case of serotonin syndrome caused by fluoxetine 20 mg and duloxetine 60 mg independently eight week apart. A 65-year old man developed fever, agitation and change of mental status after two weeks treatment with 20 mg of fluoxetine for depressive disorder. He was diagnosed unknown fever origin and discharged when fever subsided as antidepressant stopped. Eight weeks later he was prescribed 60 mg of duloxetine for the treatment of depressed mood. After 18 days on duloxetine he developed fever, agitation, myoclonus and change in mental status again. He improved rapidly after discontinuation of offending drug with supportive care. Despite serotonin syndrome is usually caused by poly-pharmacy of serotonergic drugs, this case shows unusual serotonin syndrome developed by therapeutic dose of two drugs of different classes independently.

Reporte de caso clínico: depresión, estrés y pica, ¿un nexo serotoninérgico? / Case report. Depressive illness, stress and pica: a serotoninergic link?

Tanto el CIE-10 como el DSM-IV coinciden en que la pica es la ingestión persistente de sustancias no nutritivas. Cabe señalar que ambos sistemas de clasificación incluyen a la pica dentro de los trastornos que ocurren en la infancia. Nosotros describimos el caso de una mujer de 47 años de edad sin antecedentes psiquiátricos, quien luego de una serie de eventos estresantes, presentó síntomas depresivos y ansiosos, que configuraron un diagnóstico de episodio depresivo mayor. Dentro de los exámenes realizados destaca un hemograma con alteraciones compatibles con una anemia ferropénica, por lo que se indicó el tratamiento respectivo. En los controles sucesivos, la paciente tuvo una evolución tórpida de su cuadro depresivo, y además se sumó otro fenómeno, el cual consistió en ingesta de hielo. Comiendo promedio, entre 6 a 8 cubetas de hielo diarios. Esto último se inició de manera brusca y por primera vez en su historia de vida. A pesar de la existencia de anemia en esta paciente, creemos que este hecho no explica en forma satisfactoria lo ocurrido en este caso, por lo que se intenta dar una hipótesis neurobiológica que involucra al sistema serotoninérgico. Es importante destacar que tanto la ocurrencia de pica en un adulto como la asociación de ésta con un episodio depresivo, son hechos escasamente descritos.

The ICD-10 as well as the DSM-IV, coincide in the fact that pica is the persistent eating of non nutritive substances. It should be noted. That both classification systems include pica under the disorders that occur on infancy and early childhood. We describe the case of a woman of 47 years old, without psychiatric past history that presented a depressive illness after a series of stressful events. Within the laboratory test, there was an altered cell blood count that showed an iron deficiency anemia, the reason why respective treatment was indicated. The patient had a torpid evolution of her depression and also another phenomenon appeared, she began to eat 6 to 8 ice buckets daily in average (more than 200 ice cubes) this behavior started abruptly and for the fist time in her life history. Despite the presence of anemia, we believe that this fact does not explain satisfactorily what happens in this case. That is why we try to give a neurobiological hypothesis that includes the serotonergic system. It is noteworthy that the presence of pica in an adult and its assoc8iation with a depressive illness is rarely reported.

Síndrome serotonínico pediátrico: reporte de un caso / Serotonin syndrome pediatric: case report

El síndrome serotonínico es un cuadro neurológico agudo debido a hiperactividad serotoninérgica, por la interacción de drogas que refuerzan o mimetizan la acción del neurotrasmisor. La incidencia del síndrome de serotonina es ascendente por la disponibilidad creciente de fármacos serotoninérgicos como los antidepresivos. Por ello es importante que los médicos reconozcan y manejen adecuadamente el síndrome serotonínico. Este reporte de caso se refiere a una intoxicación accidental por el neuroléptico atípico olanzapina en un niño de 2 años, quien desarrolló manifestaciones clínicas como agitación, sudoración, mioclonías, clonus espontáneo e hipertermia, considerados como criterios diagnóstico del cuadro. La terapia consistió en descontaminación interna con lavado gástrico, carbón activado y sulfato de sodio, ciproheptadina, propranolol y furosemida. Su evolución fue satisfactoria. En nuestro país hay disponibilidad de la mayoría de los fármacos causales y tienen amplio uso, por lo que es probable el subregistro del síndrome. De allí la importancia de este reporte de caso

Serotonin syndrome is an acute neurologic picture due to serotonergic hyperactivity, due to the interaction of drugs that enhance or mimic the action of the serotonin. The incidence of serotonin syndrome is rising because of the growing availability of serotonergic drugs such as antidepressants. It is therefore important that clinicians recognize and manage appropriately this syndrome. This case report refers to an accidental poisoning by the atypical neuroleptic olanzapine in a 2 year old boy who developed clinical manifestations such as agitation, sweating, myoclonus, spontaneous clonus and hyperthermia, considered as diagnostic criteria for the syndrome. Therapy consisted of internal decontamination with gastric lavage, activated charcoal and sodium sulfate, cyproheptadine, propranolol and furosemide. The clinical outcome was satisfactory. In our country the majority of the causal drugs are easily available and widely employed, for which reason it is probable that this syndrome is under registered. Hence the importance of this case report

Receptores sigma1: um novo alvo para o tratamento farmacológico da depressão? / A new target for the pharmacologycal treatment of depression?

Apesar de décadas de estudos sobre os antidepressivos (ADs), seus mecanismos de ação permanecem obscuros. Muitos ADs interagem com receptores sigma e evidências crescentes sugerem que estas proteínas medeiam efeitos antidepressivos em animais e humanos. Os receptores sigma são subdivididos em dois subtipos, sigma-1 e sigma-2. Em particular, uma potencial atividade antidepressiva foi postulada para agonistas do receptor sigma-1, os quais se localizam predominantemente no reticulo- endoplasmático de neurônios e oligodendrócitos. Os receptores sigma estão localizados em regiões cerebrais que são afetadas na depressão e são capazes de modular a atividade dos sistemas centrais de neurotransmissores, incluindo os sistemas noradrenérgico, serotonérgico, dopaminérgico e glutamatérgico (NMDA), que são considerados importantes no mecanismo de ação dos ADs conhecidos. O foco desta revisão é discutir a literatura relacionada aos receptores sigma e aos seus ligantes em relação às suas propriedades antidepressivas.

Elevated mazes as animal models of anxiety: effects of serotonergic agents

This article reviews reported results about the effects of drugs that act upon the serotonergic neurotransmission measured in three elevated mazes that are animal models of anxiety. A bibliographic search has been performed in MEDLINE using different combinations of the key words X-maze, plus-maze, T-maze, serotonin and 5-HT, present in the title and/or the abstract, with no time limit. From the obtained abstracts, several publications were excluded on the basis of the following criteria: review articles that did not report original results, species other than the rat, intracerebral drug administration alone, genetically manipulated rats, and animals having any kind of experimental pathology. The reported results indicate that the effect of drugs on the inhibitory avoidance task performed in the elevated T-maze and on the spatio temporal indexes of anxiety measured in the X and plus mazes correlate with their effect in patients diagnosed with generalized anxiety disorder. In contrast, the drug effects on the one-way escape task in the elevated T-maze predict the drug response of panic disorder patients. Overall, the drug effects assessed with the avoidance task in the T-maze are more consistent than those measured through the anxiety indexes of the X and plus mazes. Therefore, the elevated T-maze is a promising animal model of generalized anxiety and panic disorder.

No presente artigo, revisamos resultados publicados relatando efeitos de drogas que atuam na neurotransmissão serotonérgica medidos em três labirintos elevados, que são modelos animais de ansiedade. Realizamos uma busca bibliográfica no MEDLINE, usando diferentes combinações das palavras-chave: X-maze, plus-maze, T-maze, serotonin e 5-HT, presentes no título ou no resumo, sem limite de tempo. Dos resumos obtidos, vários foram excluídos com base nos seguintes critérios: artigos de revisão que não continham resultados originais, espécies diferentes do rato, apenas injeções intracerebrais, ratos geneticamente manipulados, animais com algum tipo de patologia experimental. Os resultados relatados indicam que o efeito de drogas na tarefa de esquiva inibitória desempenhada no labirinto em T elevado, bem como nos índices espaciais de ansiedade nos labirintos em X ou em forma de cruz se correlacionam com os efeitos em pacientes diagnosticados com o transtorno de ansiedade generalizada. Por outro lado, os efeitos de drogas na tarefa de fuga unidirecional do labirinto em T predizem a resposta a drogas dos pacientes com o transtorno de pânico. De modo geral, os efeitos de drogas sobre a tarefa de esquiva no labirinto em T são mais consistentes que os medidos pelos índices de ansiedade calculados nos labirintos em X e em forma de cruz. Portanto, o labirinto em T-elevado é um modelo promissor dos transtornos de ansiedade generalizada e de pânico.

Tratamiento farmacólogico de la obesidad: presente, pasado y futuro / Treatment pharmacologic of the obesity: present, past and future

La obesidad es una enfermedad endocrino-metabólica caracterizada por excesiva acumulación de grasa en el tejido adiposo. La importancia en el estudio y tratamiento de la obesidad, radica no sólo en la alta incidencia de ésta patología en los últimos años, sino el alto riesgo en salud que ésta implica. El objetivo del tratamiento es revertir el balance energético positivo, y mejoramiento de las co-morbilidades asociadas, mediante la reducción de la ingesta de alimentos y el aumento del gasto energético. Los pilares de la terapéutica son modificar la conducta, dieta y ejercicios. Sin embargo estas no son herramientas que garantizan el mantenimiento de la pérdida de peso a largo plazo sin efecto rebote. Los fármacos constituyen una herramienta empleada en asociación con los anteriores y no como única medida. Los fármacos para el tratamiento de la obesidad, se clasifican en aquellos que reducen la ingesta de alimentos (agentes noradrenérgicos, serotoninérgicos y duales), disminuyen la absorción (orlistat) y los que incrementan la termogénesis (efedrina y cafeína). En la actualidad sólo sibutramina y orlistat se vislumbran como las únicas drogas cuya seguridad y eficacia demostrada permiten su aplicación clínica a largo plazo (2 años). Los avances en el estudio del balance energético y su regulación han postulado nuevos blancos para la fabricación de futuros fármacos más espec¡ficos y eficaces como los antagonistas de receptores endocanabinoides.

Serotonergic modulation of dopamine neurotransmission a mechanism for enhancing therapeutics in schizophrenia

Although the principal mechanism by which all antipsychotic drugs act is the blockade of dopamine D-2 receptors, typical antipsychotics given in doses within the clinically effective range induce extrapyramidal symptoms [EPS]. Serotonin Hydroxytryptamine, 5-HT can modulate the activity of dopaminergic neurons, while the activity of atypical antipsychotic agent towards serotonin receptors is involved in the ability of these agents to produce fewer EPS. In order to extend therapeutics in schizophrenia, it is important to examine the serotonergic modulation of neuroleptic activity. This review analyzes differences in neurochemical, behavioral and pharmacological profiles of typical and atypical antipsychotics and the role of serotonin receptors in the attenuation of EPS-induced by the typical neuroleptics. In addition to blocking dopamine receptors, the atypical antipsychotics also have affinities for serotonin receptors. Serotonergic modulation of motor activity appears primarily of inhibitory type. Stimulation of somatodendritic 5-HT-1A receptors decreases the availability of 5-HT at inhibitory 5-HT-2C receptors located on dopaminergic neurons to attenuate acute parkinsonian-like effects of typical antipsychotics. An increase in the effectiveness of pre and postsynaptic 5-HT-1A receptors following long-term administration of haloperidol raises the possibility that 5-HT agonists may also prove useful for the alleviation of late appearing tardive dyskinesias. Clinicians can now apply the knowledge of serotonergic modulation of neuroleptic action to the treatment of schizophrenic patients by using selected serotonergic anxiolytics and antidepressants as adjuvants in the treatment of schizophrenia. This is a review article