Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline

The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p<0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline

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 ...

Sertraline inhibits formalin-induced nociception and cardiovascular responses

The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8/per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg-1·day-1, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5 percent (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7 percent), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9 percent, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

Sertralina no tratamento de pacientes com depressão maior leve e moderada: estudo multicêntrico brasileiro / Sertraline for the treatment of mild to moderate major depression: brazilian multicenter study

Introdução: O presente estudo teve por objetivo avaliar a eficácia, segurança e tolerabilidade da sertralina no tratamento de pacientes com depressão maior leve e moderada. Pacientes e métodos: Os pacientes selecionados tinham idade > 18 anos e estavam em tratamento ambulatorial. Medicamentos anteriores foram suspensos durante um período de wash-out de duas semanas. A seguir, os pacientes receberam a sertralina, na dose inicial de 50 mg/dia, até a quarta semana. A partir de então a dose diária de manutenção poderia ser aumentada até 200 mg, de acordo com a eficácia e tolerabilidade. A eficácia terapêutica foi avaliada pelos escores nas escalas Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton para Depressão (HAM-D) e de Impressão Clínica Global (ICG). Resultados: Foram avaliados quanto à segurança e à eficácia 51 pacientes (42 mulheres). O tratamento com sertralina mostrou reduções significativas dos escores nas escalas MADRS, HAM-D e ICG de 15,7±6,1; 12,2±3,9 e 3,5±0,6 para 6,2±6,5; 5,4±4,7 e 2,3±1,0 (P<0,0001). A sertralina foi bem tolerada, sendo os eventos adversos mais freqüentes desconforto gastrointestinal (N=14; 24,6), cefaléia (N=7; 12,3), alterações do sono (N=7; 12,3), tontura (N=4; 7,0) e anorexia (N=4; 7,0). Seis pacientes descontinuaram o estudo por eventos adversos. Conclusão: A sertralina se mostrou eficaz e com bom perfil de segurança e tolerabilidade no tratamento de pacientes com depressão maior leve e moderada.

Involvement of potassium channels in hypoglycemic effect of sertraline.

Effect of 21 days administration of sertraline (30 mg/kg, po) in streptozotocin (55 mg/kg, ip) induced diabetic and non-diabetic rats produced hypoglycemia in diabetic and non-diabetic rats. Pinacidil (1mg/kg, po), when co-administered with sertraline or glimepiride antagonized the decrease in glucose levels in diabetic rats. Pinacidil (10(-6)-10(-3) M) produced dose dependent relaxation (EC50-1.58 x 10(-5) M). Neither sertraline nor glimepiride had any effect on the resting tension of ileum preparation. Both sertraline and glimepiride antagonized competitively the pinacidil-induced relaxation. The pA2 values of sertraline and glimepiride reversal of pinacidil-induced relaxation were 5.5 and 6.2 respectively. These studies suggest the involvement of K+ channels in hypoglyceimic effects of sertraline.

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.

Sertralina en el tratamiento de la eyaculación precoz / Sertraline in the treatment of early ejaculation

Los tratamientos con antidepresivos frecuentemente se asocian con efectos colaterales en la esfera sexual. Aquellos que actúan inhibiendo la recapacitación de la serotonina como la sertralina retardan el orgasmo en hombres y mujeres. Se trataron con sertralina 92 pacientes, terminaron su período de observación 72 de ellos. De los pacientes que completaron tratamiento 64 de ellos refirieron estar mejor, 8 manifestaron estar igual y ninguno empeoró. La impresión de sus parejas fue de mejoría en 65 pacientes y permanecieron igual 7 casos. El tiempo de eyaculación por tratamiento fue de 2,5 minutos y el post tratamiento fue de 5,5 minutos (p<0,05). De los 64 pacientes que obtuvieron una adecuada respuesta terapéutica, 17 de ellos recidivaron durante el período final de observación, cuando ya no estaban recibiendo el medicamento. De este modo podemos concluir que la sertralina es un medicamento eficaz y seguro en el tratamiento de la eyaculación precoz, sin embargo, existe un porcentaje no despreciable de pacientes que no completa su tratamiento por diversas, razones y otro porcentaje que recidiva al suspender el tratamiento