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Publications (7)5.25 Total impact

  • E. Aksöz · S.S. Bilge · F. Ilkaya · B.D. Baş · Y. Kesim · S. Çelik
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) induced delayed ejaculation as an adverse effect. Cause of this they have been used to treat Premature Ejaculation. Recent studies have suggested that sildenafil, a selective inhibitor of cyclic GMP specific phosphodiesterase type 5, could be beneficial in the treatment of PE. However, some studies demonstrated that sildenafil is helpfull in the treatment of SSRI induced delayed ejaculation. In the present study, we examined the effects of administration of the SSRIs plus sildenafil combination on vas deferens contractions on isolated rat vas deferens. Saline (10ml/kg) was administered to the control group rats for 15 days intraperitoneally (i.p). Fluoxetine (20 mg/kg), sertraline (10 mg/kg) or citalopram (10mg/kg) were administered to the SSRI groups for 14 days i.p and 10 ml/kg saline was administered at 15th day. SSRIs were administered to the combination groups for 14 days i.p. and 10 ml/kg sildenafil was administered at 15th day. Saline (10ml/kg) was administered to the sildenafil group for 14 days i.p and at 15th day, 10 mg/kg sildenafil was administered. Rats were exposed to the forced swimming test. After the test rats vas deferens were removed and placed in organ baths and the contraction responses induced by electrical field stimulation (EFS) were recorded. The contraction responses induced by EFS were inhibited by SSRIs. This inhibition effect was antagonized by sildenafil when administered with fluoxetine or citalopram but not with sertraline. The results thought that sildenafil could have limited the 5-HT increasing effects of fluoksetin and citalopram, having lower potency for binding to the 5-HTT in synaptic cleft, whereas could not have limited this effect of sertraline, having more potency for binding to the 5-HTT. We suggest that 5-HTT may have a role on differantiated effects of SSRIs plus sildenafil combination on vas deferens contractions.
    No preview · Article · Jan 2009 · Ondokuz Mayis Universitesi Tip Dergisi
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    ABSTRACT: Echo-planar magnetic resonance imaging (EP-MRI), which is novel variant of MRI, is thought to have antidepressant properties in humans and animal models. Using the forced swimming test (FST), we investigated which monoaminergic system in mice is affected by EP-MRI. The short- and long-term effects of EP-MRI on immobility time in the FST and motor activity within a locomotor activity cage were examined. Two groups of mice underwent 20 min of EP-MRI in an MR scanner (Siemens, 1.5 T Symphony) either 23.5 or 1 h before the start of the second session of the FST. In both groups, the immobility duration in the FST was reduced, similar to effective antidepressant drug treatments. Climbing behavior in the 1-h group and swimming behavior in the 23.5-h group increased significantly, similar to that seen after the administration of desipramine (a noradrenaline reuptake inhibitor) and sertraline (a selective serotonin reuptake inhibitor), respectively. The findings support the hypothesis that EP-MRI has an antidepressant-like effect. We suggest that the antidepressant-like effect begins in the early period with noradrenaline systems and is maintained in the late period with serotonin systems.
    No preview · Article · Sep 2008 · Brain Research
  • E. Aksöz · S.S. Bilge · M. Kukt · Y. Kesim · S. Çelik
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    ABSTRACT: Phosphodiesterease type 5 (PDE5), nitric oxide synthase (NOS) and guanilate cyclase have shown high activity in areas responsible to behaviours in brain. It is alleged that PDE5 inhibitor sildenafil which is used in erectile disfunction passes blood brain barrier and can cause adverse effects related to behaviours. The aim of this study, to investigate the effect of sildenanil in depression by forced swimming test in mice. We administered sildenafil (1, 5, 10, 15, 20, 30 mg/kg), sertraline (20 mg/kg) and imipramine (30 mg/kg) with intraperitoneal (ip) injection. All drugs were injected 15 min. before testing. Sertraline and imiprarnine given alone and in combination with sildenafil. When combination with sildenafil and other drugs were employed, other drugs were administered 10 min. before sildenafil. The activity of each mice was recorded for 5 min. in an activity cage (Ugo Basile, 7430-Varese, Italy). Then immobility was measured during the last 4 min. of the 6 min. swim test. Increase immobility time in a swim test has been found to represent "depression- like" behaviour. Sildenafil at a dose of 10mg/kg increased the immobility time without affecting locomotor activity (p<0.05). imiprarnine and sertraline significantly decreased the immobility time (p<0.05). The depressant-like effect of sildenafil (10 mg/kg) was prevented by pretreatment with both sertraline and imiprarnine (p<0.05). These findings suggest that, sildenafil has a depressant-like effect on the forced swimming test and NO-cGMP pathway may play a role in depression.
    No preview · Article · Jan 2006 · Ondokuz Mayis Universitesi Tip Dergisi
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    S Sirri Bilge · Yuksel Kesim · Mehmet Kurt · Elif Aksoz · Suleyman Celik
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    ABSTRACT: To evaluate the effect of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-selective type 5 phosphodiesterase, on isolated rat vas deferens and its connections with the purinergic system. Epididymal and prostatic portions of isolated vas deferens were placed in organ baths containing Krebs' solution. Contractions were induced by noradrenaline (NA), adenosine triphosphate (ATP), alpha,beta-methylene ATP and electrical field stimulation (EFS). The effect of sildenafil on the contractions was compared with suramin and Evans blue (EB). NA, ATP, alpha,beta-methylene ATP and EFS caused contractions in both portions of vas deferens. NA-induced contractions were unaffected by sildenafil and suramin but potentiated by EB. ATP-induced contractions were non-competitively inhibited in both portions by sildenafil and suramin but potentiated by EB. alpha,beta-methylene ATP-induced contractions were unaffected by sildenafil but were inhibited in both portions by suramin and EB. EFS-induced contractions were inhibited by sildenafil and suramin while potentiated by EB. Sildenafil inhibited the contractions in both portions of vas deferens, as did suramin. We have suggested that purinergic system has a role in this antagonism and it seems to be mediated by an ATP-dependent mechanism instead of a receptor interaction.
    Preview · Article · Oct 2005 · International Journal of Urology
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    ABSTRACT: Several studies have shown a role of nitric oxide/cyclic guanosine monophosphate signaling pathway in the regulation of anxiety. The effects of the phosphodiesterase (PDE) 5 inhibitors on anxiety are not fully understood. The aim of present study was to investigate the possible role of sildenafil, an inhibitor of cyclic GMP-specific phosphodiesterase, on anxiety in the plus-maze test in mice. Sildenafil at a dose of 0.5 mg/kg had no significant effect on the behavior in the plus-maze test but at doses of 1 and 3 mg/kg induced an anxiogenic effect. The combination of sildenafil (1 mg/kg, i.p.) and methylene blue (1 mg/kg, i.p.) abolished the anxiogenic-like effect of sildenafil. The combination of sildenafil (1 mg/kg, i.p.) and L-arginine (50 mg/kg, i.p.) decreased the percentage of time spent in open arms compared to saline-treated group. Diazepam at a dose of 2 mg/kg significantly increased the percentage of time spent in open arms (p < 0.05). Sildenafil at a dose of 3 mg/kg and the combination of L-arginine (50 mg/kg, i.p.) and sildenafil (1 mg/kg, i.p.) significantly decreased the locomotor activity (p < 0.05). These results suggest that a nitric oxide-cGMP pathway seems to play an important role in sildenafil-induced anxiogenic-like effect.
    Full-text · Article · Jan 2004 · Polish journal of pharmacology
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    Mehmet Kurt · S Sirri Bilge · Osman Kukula · Suleyman Celik · Yuksel Kesim
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    ABSTRACT: The present study was performed to investigate the effect of propofol on anxiety using the elevated plus-maze test. Groups of mice received propofol (20, 40, 60 mg/kg) or diazepam (2 mg/kg), caffeine (30 mg/kg), L-arginine (100 mg/kg), m-chlorophenylpiperazine (m-CPP, 2.5 mg/kg) and then were placed in an elevated plus-maze that was composed of two opposite closed arms and two opposite open arms. Propofol (20, 40, 60 mg/kg) and diazepam (2 mg/kg) significantly increased the percentage of time spent in the open arms compared to control. Caffeine (30 mg/kg) and m-CPP (2.5 mg/kg) decreased the percentage of time spent in the open arms and these effects were antagonized when propofol (40 mg/kg) was administered before the test. L-arginine (100 mg/kg) has also produced anxiogenic effect and this effect was not prevented by propofol. All drugs used in this study did not significantly change locomotor activity. These results suggest that propofol has anxiolytic effect in plus-maze test.
    Full-text · Article · Nov 2003 · Polish journal of pharmacology
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    ABSTRACT: The effects of N-nitro-L-arginine-methyl ester (L-NAME) a nitric oxide (NO) synthase inhibitor and L-arginine, a NO precursor, were investigated on lidocaine-induced convulsions. In the first experiment, four groups of mice received physiological saline (0.9%), L-arginine (300 mg/kg, i.p.), L-NAME (100 mg/kg, i.p.) and diazepam (2 mg/kg), respectively. Thirty minutes after these injections, all mice received lidocaine (50 mg/kg, i.p.). In the second experiment, four groups of mice received similar treatment in the first experiment, and 30 min after these injections, all mice received a higher dose of lidocaine (80 mg/kg). L-NAME (100 mg/kg, i.p.) and diazepam (2 mg/kg) significantly decreased the incidence of lidocaine (50 mg/kg)-induced convulsions. In contrast, the L-arginine treatment increased the incidence of lidocaine (80 mg/kg, i.p.)-induced convulsions significantly. These results may suggest that NO is a proconvulsant mediator in lidocaine-induced convulsions.
    No preview · Article · Feb 2001 · The Japanese Journal of Pharmacology