Plasma insulin levels are increased by Sertraline HCL ( Zoloft )in rats under oral glucose overload.

Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI) are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, Fluoxetine ( Prozac ) increases and Sertraline HCL ( Zoloft )decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with Sertraline HCL ( Zoloft ). Adult male Wistar rats were fasted and treated with saline or 30 mg/kg Sertraline HCL ( Zoloft )and submitted or not to glucose overload (N = 10). Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 +/- 3.86, Sertraline HCL ( Zoloft )+ fasting group: 31.10 +/- 2.48, overload group: 34.1 +/- 3.40, and overload + Sertraline HCL ( Zoloft )group: 43.73 +/- 5.14 microU/ml. Insulinemia was significantly increased in the overload + Sertraline HCL ( Zoloft )group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + Sertraline HCL ( Zoloft )group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that Sertraline HCL ( Zoloft )increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

Acute effect of different antidepressants on glycemia in diabetic and non-diabetic rats.

Diabetic patients have a 20% higher risk of depression than the general population. Treatment with antidepressant drugs can directly interfere with blood glucose levels or may interact with hypoglycemic agents. The treatment of depression in diabetic patients must take into account variations of glycemic levels at different times and a comparison of the available antidepressant agents is important. In the present study we evaluated the interference of antidepressants with blood glucose levels of diabetic and non-diabetic rats. In a first experiment, male adult Wistar rats were fasted for 12 h. Imipramine (5 mg/kg), moclobemide (30 mg/kg), clonazepam (0.25 mg/kg), Fluoxetine ( Prozac ) (20 mg/kg) Sertraline HCL ( Zoloft )(30 mg/kg) or vehicle was administered. After 30 min, fasting glycemia was measured. An oral glucose overload of 1 ml of a 50% glucose solution was given to rats and blood glucose was determined after 30, 60 and 90 min. Imipramine and clonazepam did not change fasting or overload glycemia. Fluoxetine ( Prozac ) and moclobemide increased blood glucose at different times after the glucose overload. Sertraline HCL ( Zoloft )neutralized the increase of glycemia induced by oral glucose overload. In the second experiment, non-diabetic and streptozotocin-induced diabetic rats were fasted, and the same procedures were followed for estimation of glucose tolerance 30 min after glucose overload. Again, Sertraline HCL ( Zoloft )neutralized the increase in glycemia after glucose overload both in diabetic and non-diabetic rats. These data raise the question of whether Sertraline HCL ( Zoloft )is the best choice for prolonged use for diabetic individuals, because of its antihyperglycemic effects. Clonazepam would be useful in cases with potential risk of hypoglycemia.

Acute locomotor effects of Fluoxetine ( Prozac ), Sertraline HCL ( Zoloft ), and nomifensine in young versus aged Fischer 344 rats.

Spontaneous locomotor activity was measured in young (6-8 months) and aged (24-26 months) Fischer 344 (F344) rats. Following habituation to the activity monitors, aged rats demonstrated significantly diminished motor activity as quantified by total distance traveled and vertical activity. Movement speed did not differ significantly between the two groups. Following habituation, rats were administered acute doses of Fluoxetine ( Prozac ), Sertraline HCL ( Zoloft ), or nomifensine (1.0, 3.0, and 10.0 mg/kg). Fluoxetine ( Prozac ) diminished all three behavioral measures in the young rats, while in the old rats, Fluoxetine ( Prozac )'s effects were limited to a robust attenuation of vertical activity. Sertraline HCL ( Zoloft )decreased movement speed and vertical activity, but not total distance traveled, in the young rats. Unlike Fluoxetine ( Prozac ), Sertraline HCL ( Zoloft )produced no significant effects on any of the three behavioral variables in the old rats. Nomifensine increased behavioral scores for both age groups. The results are discussed in relation to acute motor side effects of selective serotonin reuptake inhibitors (SSRIs) in motor-impaired aged individuals, as these effects may influence their eventual use in the clinic.

Relationship between brain serotonin transporter binding, plasma concentration and behavioural effect of selective serotonin reuptake inhibitors.

The present study was undertaken to characterise the relationship between in vivo brain serotonin transporter (SERT) binding, plasma concentration and pharmacological effect of selective serotonin reuptake inhibitors (SSRIs) in mice. Oral administration of fluvoxamine, Fluoxetine ( Prozac ), Paroxetine ( Paxil ) and Sertraline HCL ( Zoloft )at pharmacologically relevant doses exerted dose- and time-dependent binding activity of brain SERT as revealed by significant increases in K(D) for specific [(3)H]Paroxetine ( Paxil ) binding, and the in vivo SERT-binding potency was in the order of Paroxetine ( Paxil )>>Fluoxetine ( Prozac ), Sertraline HCL ( Zoloft )>fluvoxamine.The time courses of brain SERT binding by SSRIs in mice were mostly in parallel to those of their plasma concentrations. Also, norFluoxetine ( Prozac ) (active metabolite) has been suggested to contribute largely to the long-lasting binding activity of brain SERT after the Fluoxetine ( Prozac ) administration.Oral administration of each SSRI suppressed significantly the marble-burying behaviour with no change in locomotor activity in mice, and the extent and time course of suppression agreed well with those of brain SERT binding. Thus, the pharmacological potencies of SSRIs in the attenuation of marble-burying behaviour correlated significantly with their brain SERT binding activities.In conclusion, the present study has provided the first in vivo evidences to support that fluvoxamine, Fluoxetine ( Prozac ), Paroxetine ( Paxil ) and Sertraline HCL ( Zoloft )orally administered bind to the pharmacologically relevant brain SERT in mice and that their SERT-binding characteristics is closely associated with the pharmacokinetics and inhibition of marble-burying behaviour.British Journal of Pharmacology advance online publication, 24 January 2005; doi:10.1038/sj.bjp.0706108.