Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

The effect of Sertraline, Paroxetine, Fluoxetine and Escitalopram on testicular tissue and oxidative stress parameters in rats

Introduction: The aim of this study was to evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on testicular tissue and serum malondialdehyde (MDA) levels in rats. Materials and methods: A total of 40 male Wistar albino rats, 5.5-6 months old, were equally divided at random into five groups: group 1 was the control group, group 2 received sertraline 10mg/kg (p.o), group 3 was administered fluoxetine 10mg/kg (p.o), group 4 received escitalopram 10mg/kg (p.o), and group 5 (n = 8) was administered paroxetine 20mg/kg. Each dose was administered orally for two months. Johnsen’s criteria were used to categorize spermatogenesis. Johnsen’s method assigns a score of 1 to 10 to each tubule cross-section examined. In this system, a Johnsen score of 9 and 10 indicates normal histology. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were evaluated. Serum MDA levels were also measured. Results: The mean Johnsen scores were 9.36 ± 0.33, 9.29 ± 0.32, 8.86 ± 0.48, 9.10 ± 0.56, and 8.33 ± 0.90 in control group, sertraline group, fluoxetine group, escitalopram group, and paroxetine group, respectively. The Johnsen score was significantly lower for paroxetine group compared with the control group (p < 0.05). The mean FSH level increased only in the sertraline group. With the exception of the fluoxetine group, the testosterone levels were lower in all groups compared with the control group. The total testosterone level was significantly lower in the sertraline group compared with the control group [40.87 (22.37-46.8) vs. 15.87 (13.53-19.88), p < 0.01]. There were no significant differences between the groups with respect to the MDA and LH levels (p = 0.090 and p = 0.092). Conclusion: These data suggest that SSRIs have a negative effect on testicular tissues. This negative impact is markedly greater in the paroxetine group. To determine the exact ...

Anti-depressant like activity of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) a 5-HT3 receptor antagonist.

The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.

Warfarin: pharmacological profile and drug interactions with antidepressants / Varfarina: perfil farmacológico e interações medicamentosas com antidepressivos

Oral anticoagulants are among the drugs with the greatest number of drug interactions. The concomitant use of several medications is a common practice in patients with cardiovascular problems, who often also present with depression; therefore, the probability of an interaction occurring between warfarin and the antidepressants is high, and may result in increased or decreased anticoagulant activity. Since the possible interactions between these two classes of drugs have been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.

Os anticoagulantes orais estão entre as drogas com maior número de interações medicamentosas. O uso concomitante de vários medicamentos é uma prática comum em pacientes com problemas cardiovasculares, os quais frequentemente também apresentam depressão; assim, a probabilidade de ocorrer alguma interação entre a varfarina e os antidepressivos é bem expressiva, podendo resultar em um aumento ou uma diminuição da atividade anticoagulante. Como as possíveis interações entre essas duas classes de medicamentos se mostraram pouco exploradas na literatura, com risco aos pacientes que fazem uso delas, revisamos a farmacologia da varfarina e suas possíveis interações com antidepressivos. Dos antidepressivos analisados, os que apresentaram efeitos relevantes na interação com a varfarina foram, em ordem decrescente: paroxetina, venlafaxina, fluoxetina e duloxetina.

Refluxo gastroesofágico participando da cascata cognitiva do pânico / Gastroesophageal reflux participating on panic cognitive cascade

O transtorno do pânico (TP) é um transtorno ansioso não-fóbico que acomete de 1,5% a 4% da população mundial. É caracterizado por ataques imotivados de mal-estar psíquico e sintomas somáticos, além de ansiedade antecipatória à crise, com prejuízo funcional ao indivíduo. O objetivo deste relato de caso é descrever a associação entre transtorno do pânico e doença do refluxo gastroesofágico (DRGE). MCL, 25 anos, apresentava crises de pânico frequentes, pouco responsivas ao tratamento durante 6 meses, mesmo com readequação da farmacoterapia. Iniciou-se investigação, sendo fechado o diagnóstico de DRGE, cujo tratamento culminou em remissão das crises de pânico. A dor torácica aguda da DRGE era interpretada como ameaça proximal, ocasionando dúvidas sobre passar mal e hiperventilação, servindo como gatilho da cascata cognitiva do pânico, no mesencéfalo dorsal. A inflamação da mucosa esofágica funciona como ameaça distal, estimulando a amígdala e causando ansiedade antecipatória, mantendo a elevação dos hormônios de estresse. Segundo o modelo de Deakin-Graeff, embora a 5-HT iniba o ataque de pânico e facilite a ansiedade antecipatória, no TP esta última é estimulada por meio do núcleo dorsal da rafe. Portanto, casos que incluem a associação TP e DRGE devem ser mais bem examinados, para que haja diagnóstico e tratamento adequados.

Panic disorder (PD) is a non phobic anxiety disorder that affects 1,5 to 4% worldwide. It is characterized by unmotivated acute attacks, with mental and somatic symptoms, and by an anxiety which precedes the crises, resulting in functional disturbance. The objective of this case study is to describe the association between PD and gastroesophageal reflux (GR). MCL, 25 years, presented with frequent panic crises, with low response to the therapy for 6 months, even after modification of medication doses. Investigation was carried out and diagnoses defined as GR. The treatment resulted with elimination of the panic crises. The acute thoracic pain of the GR is interpreted as a near threat, causing uncertainty regarding an unwell feeling with hyperventilation, acting as a trigger of the panic cognitive cascade, in the dorsal mesencephalon. The esophagic mucosa inflammation is interpreted as a distal threat, stimulating the amygdale and generating anticipated anxiety, increasing stress hormones. According to Deakin-Graeff model, even though 5HT inhibits the panic attack and stimulates the anticipated anxiety, the panic disorder stimulates the latter through dorsal raphe nucleus. In conclusion, the association between PD and GR should be better identified in order that the correct diagnosis and adequate treatment is achieved.

La evaluación de los efectos terapéuticos de Paroxetina en el síndrome depresivo endógeno / The evaluation of the Paroxetine therapeutic effects in the endogenous depressive syndrome

Objetivo. Evaluación de los efectos terapéuticos de Paroxetina en depresión mayor mediante escalas psicológicas y estudios psiquiátricos en pacientes. Método. La muestra objeto de estudio estaba compuesta por 99 pacientes tratados con Paroxetina por depresión mayor. El grupo control estaba constituido por 98 pacientes tratados con Sulpiride por depresión mayor. Los datos del estudio provienen de las historias clínicas de los pacientes. Todos ellos fueron evaluados mediante la escala de depresión de Hamilton de 24 ítems y el inventario de depresión de Beck, así como con la escala de depresión de Montgomery-Asberg. Los efectos del tratamiento fueron evaluados con la aplicación de dichas escalas y por medio de estudios clínicos en pacientes. Resultados. Generalmente se observó una mejoría terapéutica en alrededor del 80 por ciento de los pacientes tratados con Paroxetina. La puntuación media en la Escala de Hamilton disminuyó a causa del tratamiento del punto 46,2 al 17,4. Después del tratamiento con Paroxetina de una depresión mayor la disminución de puntuación en la escala de Hamilton fue del 90,6 por ciento (depresiones leves), el 64,1 por ciento (depresiones moderadas) y el 57,4 (depresiones mayores). Se notó una mejoría en episodios de depresión mayor como consecuencia del tratamiento con Paroxetina en un 47,47 por ciento de pacientes (la remisión completa sostenida de la depresión), en un 6,06 por ciento de los pacientes hubo una mejoría sustancial, en un 20,20 por ciento de los pacientes mejoría moderada y en un 6,06 pacientes mejoría leve...(TRUNCADO)

Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced catalepsy in mice

Depression found in Parkinson disease (PD) usually responds to selective serotonin reuptake inhibitors (SSRIs). Drugs that modify experimental neuroleptic catalepsy (NC) might affect extrapyramidal symptoms in PD. Therefore, the effects of SSRIs on NC were tested in mice, 26-36 g, separated by sex. Catalepsy was induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals using a bar test. An SSRI (sertraline, ST; paroxetine, PX; fluoxetine) or vehicle (C) was injected ip 30 min before H. Dunnett's test was used for comparison of means. ST (1-5 mg/kg) or PX (1-5 mg/kg) attenuated NC, with a similar inhibition found in both sexes (5 mg/kg, 180 min: ST - males: 124 ± 10 vs 714 ± 15 s in C; females: 116 ± 10 vs 718 ± 6 s in C; PX - males: 106 ± 10 vs 714 ± 14 s in C; females: 102 ± 10 vs 715 ± 14 s in C). At 0.3 mg/kg, neither of these drugs affected NC. Fluoxetine (1-25 mg/kg) also inhibited catalepsy, although the effect was not dose-dependent; no differences were observed between males and females (5 mg/kg, 180 min: males, 185 ± 14 vs 712 ± 14 s in C; females, 169 ± 10 vs 710 ± 19 s in C). For these SSRIs, maximal inhibition of NC was obtained with 5 mg/kg, 180 min after H. These results are consistent with the hypothesis that serotonergic mechanisms modulate nigrostriatal transmission, and suggest that SSRIs are possibly safe in depressive PD patients.

Effects of antidepressants on morphine withdrawal

The acute and chronic effects of paroxetine and fluoxetine on naloxone- withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluoxetine [25 mg/kg, s.c., given 30 min prior to naloxone withdrawal pairing] and chronic daily paroxetine [10 mg/kg, s.c.] co-administration with a morphine induction protocol, both attenuated morphine withdrawal place aversion. Conversely, acutely administered paroxetine [up to 25 mg/kg, s.c.] or chronic daily fluoxetine [10 mg/kg, s.c.] co-administration with morphine did not modify subsequent withdrawal place aversion. Previous radiologand binding studies have indicated that fluoxetine has opioid-displacing properties. It is suggested therefore that acute fluoxetine may have decreased withdrawal aversion, probably through serotonin and also, in part, via an opioid-like mechanism whereas chronic paroxetine decreased withdrawal aversion by a serotonergic mechanism, but it is not clear whether opioid systems play any role in the action of paroxetine

Dos inhibidores de recaptación de serotonina en eyaculación precoz / 2 serotonin reuptake inhibitors in premature ejaculation

La eyaculación precoz es muy frecuente, pero sólo consultan aquellos hombres que lo sienten como problema. Los inhibidores de la recaptacción de Serotonina actuan a nivel de la vesícula sináptica impidiendo la recaptación del neurotransmisor, permitiendo así una mayor utilización por la neurona sináptica

Actualización de psicofarmacología de la depresión / An update on depression psychopharmacology

Se analizan los diferentes grupos de fármacos de acción antidepresiva según su estructura química: tricíclicos, tetracíclicos, inhibidores de la monoamino-oxidasa (MAO) y los no clasificables. Se establecen los mecanismos de acción sobre los neurotransmisores cerebrales, según una clasificación bioquímica. Se enfatiza la importancia que el médico clínico se base en la sintomatología depresiva del enfermo según una clasificación sintomática, para la elección del fármaco a usar. Se analizan los efectos colaterales y las contraindicaciones que tienen mayor importancia en el uso de los fármacos antidepresivos según el tiempo de enfermo y según la patología concomitante. Se reseñan los tratamientos de las diferentes formas de depresión, señalando algunas instrucciones especiales que deben considerarse en cada caso