Nuri Ihsan Kalyoncu

The effects of paroxetine on rat isolated vas deferens

The aim of the present study is to evaluate whether paroxetine (a selective serotonin re-uptake inhibitor) can modify the contractile responses of isolated vas deferens. Some contractile agents, potassium chloride (KCl), adenosine 5-triphosphate (ATP), noradrenaline (NA), and electrical field stimulation (EFS) caused contractions both in epididymal and prostatic portions of vas deferens. Paroxetine (PX) in concentrations 10(-7) and 10(-6)M potentiated the contractions to KCl and ATP only in epididymal portion but in higher concentrations (10(-5) and 10(-4)M) inhibited the responses in both portions. NA responses were inhibited by PX in all concentrations used, both in prostatic and epididymal portions. Prazosin (PR), an alpha adrenergic receptor blocking agent, inhibited PX-induced potentiation observed for higher concentrations of KCl. PR also inhibited PX-induced potentiation on the responses to ATP in epididymal portion. Pretreatment with PX (10(-7) to 10(-6)M) increased the contractions to EFS but in 10(-5) and 10(-4)M concentrations inhibited them. Even though the preparations were washed out, the inhibited responses of contractile agents could not be restored. After a washout period for PX, when Bay K 8644 (calcium channel activator) was added to the bath medium, the contractile responses to KCl were partially restored. In calcium-free medium, KCl caused contractions in concentrations higher than 80 mM with lower amplitudes which were not affected by PX. Reserpinization did not change the inhibitory pattern of PXs effect on exogenously applied NA in all concentrations tested. In reserpinized rats, the potentiation caused by PX in exogenously applied ATP responses was not observed. In conclusion, we can say that PX has two different effects: inhibition and potentiation of contractions to various agonists. The inhibitory effect of the drug can be explained by a calcium channel blocking activity. The potentiating effect of the drug is mainly related to its presynaptic action, such as NA re-uptake inhibitory effect.

Effects of the celecoxib on the acute necrotizing pancreatitis in rats.

The investigation of the effects of the celecoxib as a cylooxygenase-2 (COX-2) inhibitor on the course of the acute necrotising pancreatitis (ANP) in rats. ANP was induced in 72 rats by standardized intraductal glycodeoxycholic acid infusion and intravenous cerulein infusion. The rats were divided into four groups (six rats in each group): Sham + saline, sham + celecoxib, ANP + saline, ANP + celecoxib. Six hours later after the ANP induction, celecoxib (10 mg/kg) or saline was given i.p. In the 12th hour, routine cardiorespiratuar, renal parameters were monitored to assess the organ function. The serum amylase, alanine amino transferase (ALT), interleukin 6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, the serum concentration of the urea, the tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lungs were measured. The pancreas histology was examined. In the second part of the study, 48 rats were studied in four groups similar to the first part. Survival of all the rats after the induction of ANP was observed for 24 h. The induction of the pancreatitis increased the mortality from 0/12, in the sham groups to 4/12 (30%) in the acute pancreatitis with saline group, 5/12 (42%) in the acute pancreatitis with celecoxib group respectively, heart rate, the serum activities of amylase, ALT, the tissue activities of MPO, MDA in the pancreas and lung, and LDH in BAL fluid, the serum concentration of the urea and IL-6, the degree of the pancreatic damage and decreased the blood pressure, the urine production, pO2 and the serum concentration of calcium. The use of celecoxib did not alter these changes except the serum IL-6 concentration, urine production and MPO, MDA activities in the tissue of the lungs and pancreas. Serum urea concentration and pancreatic damage in ANP + celecoxib group were insignificantly lesser than ANP + saline group. Whereas treatment with celecoxib improves lung and renal functions, the degree of pancreatic damage partially and the serum IL-6 level completely, it does not improve the cardiovascular and liver functions, the mortality rate and the calcium level. Celecoxib may be useful for the support of some organ functions during ANP in rats.

Effect of gender on antinociceptive effect of paroxetine in hot plate test in mice.

PURPOSEnMany studies have reported both a gender difference in the rates of depression and its treatment by using any of the widely used antidepressant drug groups. Some studies suggest that females respond more poorly to tricyclic antidepressants than males and appear to respond better to selective serotonin reuptake inhibitors (SSRI). There is no study investigating the analgesic/antinociceptive effects of antidepressant drugs on the basis of gender difference. In this study, we aimed to investigate the antinociceptive effect of paroxetine on the basis of gender difference.nnnMETHODSnThe antinociceptive effect of paroxetine was tested using hot plate test in Balb/c mice (30-40 g). The animals were divided into eight groups on the basis of gender.nnnFINDINGSnWhile paroxetine did not induce an antinociceptive effect in both sex at a dose of 1 mg kg(-1), it showed significant antinociceptive effects in both sex at a dose of 5 or 10 mg kg(-1). None of the doses of paroxetine revealed a gender difference in its antinociceptive action.nnnCONCLUSIONnThere are several studies showing positive or negative evidence on the gender difference of paroxetines antidepressant effect, but in the literature there is no study about the gender difference of paroxetines or any other SSRI drugs antinociceptive effect. In conclusion, our results do not show any gender difference in antinociceptive effect of paroxetine that may be important especially when it would be used as an adjuvant agent in some painful conditions.

Psychotropic drugs in pregnancy: a case-control study

Psychotropic drug exposure during pregnancy is a common problem. Among the 601 cases exposed to drugs during pregnancy, who were followed by our Toxicology Information and Follow-up Service, 124 cases had used psychotropic drugs for depression, anxiety, or psychotic disorders. As the control group, 248 women, who did not use any drugs were selected. Of the 124 cases, 80 (64.5%) had healthy babies, and 17 (13.7%) decided to terminate the pregnancy. Spontaneous abortions, intrauterine death (in the 38th week) and premature deliveries were observed in the 9 (7.3%), 1 (0.8%) and 3 (2.4%) cases, respectively, in the drug exposure group. Pregnancies of the 14 (11.3%) cases were continuing during the preparation of this manuscript. Of the 248 controls, 151 (60.9%) had healthy babies, 9 (3.6%) experienced spontaneous abortion and 3 (1.2%) decided to terminate their pregnancies, 3 (1.2%) had premature deliveries, and we observed one (0.4%) congenital abnormality, 81 (32.7%) cases were still pregnant. Odds Ratio (95% confidence interval) for spontaneous abortion was found to be 1.35 (1.27-11.82) in the cases exposed to psychotropic drugs (P=0.02). No developmental problems were observed in the babies followed for 12 months. These data may give information about the early- but not the late-term effects of psychotropic drugs used in pregnant women.

Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats.

The aim of this study was to investigate the influence of N-acetylcysteine (NAC) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increase in mortality rate, pancreatic necrosis and serum activity of amylase, alanine aspartate transferase (ALT), interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and significant decrease of concentrations of calcium, blood pressure, urine output and pO2. The use of NAC inhibited the changes in urine output, pO2, tissue activity of MPO and MDA in pancreas and lungs, and the serum activity of IL-6, ALT, and serum concentrations of urea and calcium. NAC reduced the mortality and pancreatic damage. The use of NAC has a beneficial effect on the course of ANP in rats. It may be used in the treatment of acute pancreatitis.

Paroxetine inhibited the relaxations induced by EFS in mice corpus cavernosum: is it a NOS inhibition?

Selective serotonin reuptake inhibitors are used in the treatment of psychiatric disorders but are associated with high incidence of sexual dysfunction such as ejaculation disorders by sertraline and fluoxetine, erection disorders by paroxetine. The aim of this study is to evaluate the effects of paroxetine, sertraline and fluoxetine on relaxation of smooth muscle of corpus cavernosum on the basis of nitric oxide (NO). Male mice were killed by cervical dislocation and their penile tissues were immediately removed. The tissues were incubated in organ baths containing Krebs solution at 37°C and bubbled with 95% O2 and 5% CO2. The corpus cavernosum strips were contracted with 10−5u2003m phenylephrine (PHE) and relaxed with either paroxetine, sertraline, fluoxetine (10−8–10−4u2003m) or electrical field stimulation (EFS). The effects of paroxetine, sertraline and fluoxetine were examined on EFS‐induced relaxations. While paroxetine did not show any effect on the corpus cavernosum strips precontracted with PHE, sertraline and fluoxetine caused a relaxation at concentrations of 3u2003×u200310−5–10−4u2003m. The relaxations induced by sertraline and fluoxetine were completely abolished by l‐NAME, but not d‐NAME. The relaxations induced by EFS could be inhibited by l‐NAME but not d‐NAME. Paroxetine inhibited the relaxations at high concentrations. l‐Arginine potentiated the relaxations induced by EFS; however in the presence of paroxetine these relaxations were not observed. In contrast, sertraline (10−8–10−5u2003m) and fluoxetine (10−8–10−5m) increased the relaxations induced by EFS. Sertraline and fluoxetine seem to be releasing some relaxing factor(s) and this factor may be NO. Paroxetine probably has a NOS inhibitory activity either on nNOS or eNOS, in contrast to sertraline and fluoxetine.

Ketanserin inhibits digoxin‐induced arrhythmias in the anaesthetized guinea‐pig

Abstract— Digoxin inhibits the membrane‐bound ATPase enzyme, resulting in a rise in intracellular sodium and activated outward potassium current, predisposing to arrhythmias. In this study, the effect of ketanserin, thought to block outward potassium currents, was investigated on digoxin‐induced arrhythmias. Twenty‐four guinea‐pigs were studied in four groups (control, ketanserin 0.5 mg/kg, ketanserin 1 mg/kg, ketanserin 2 mg/kg). Under pentobarbital anaesthesia (40 mg/kg), 15 min after injection of saline or ketanserin, digoxin (0.6 mg/kg) was administered through the jugular vein. Carotid artery blood pressure and electrocardiogram (ECG) were recorded. The time for the onset of the first arrhythmia and incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and premature ventricular contraction (PVC) were determined. Arrhythmias were scored according to the MacLeod scale. Ketanserin produced minor haemodynamic effects and lacked, by itself, arrhythmogenic effects at the doses studied. However, it increased the time for the onset of the first digoxin‐induced arrhythmia and decreased the incidence of VT, VF and PVC. We conclude that ketanserin inhibits digoxin‐induced arrhythmias in guinea‐pigs.

Long-term use of sertraline leads to alterations in contractility of rat isolated vas deferens

Previous experiments with rat isolated vas deferens have shown that sertraline pretreatment inhibits contractile responses to noradrenaline, KCl, serotonin and electrical field stimulation. In the present study, the aim was to investigate the effects of long-term use of sertraline on contractile responses of rat isolated vas deferens. Fifteen Sprague-Dawley rats were given long-term (21xa0days) sertraline treatment, while another 15 were used as control. Both vas deferens were excised. Epididymal and prostatic segments of each underwent electrical field and chemical stimulation (noradrenaline, serotonin, acetylcholine, adenosine-triphosphate). Epididymal and prostatic segments had different contraction characteristics. Long-term sertraline treatment inhibited contractile responses of vas deferens segments to electrical field stimulation. The responses to noradrenaline were amplified with a left shift on both segments. Responses to serotonin had only a left shift on epididymal segments, while no contractile responses were observed on prostatic segments of the groups. Long-term treatment with sertraline had peripheral effects on rat vas deferens contractility, and some of the effects may be through mechanisms other than the inhibition of serotonin re-uptake.