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    Effects of chronic L-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum
    (Polish Acad Sciences Inst Pharmacology, 2016) Yildirim, Seniz; Fincan, Gokce Sevim Ozturk; Isli, Fatma; Ercan, Sevim; Sarioglu, Yusuf
    Background: Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of L-DOPA induces yawning and penile erection in some species. The possible effects of L-DOPA on nitric oxide (NO)-dependent and-independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study. Methods: Thirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n = 4), 3 mg/kg/day (low dose) L-DOPA-injected groups (n = 6) and 12 mg/kg/day (high dose) L-DOPA-injected groups (n = 6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed. Results: The two-week treatment with high-dose L-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week L-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls. Conclusions: The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following L-DOPA administration. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.
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    Synthesis, structural characterization and myorelaxant activity of 4-naphthylhexahydroquinoline derivatives containing different ester groups
    (Serbian Chemical Soc, 2016) Gunduz, Miyase Gozde; Albayrak, Emine; Isli, Fatma; Fincan, Gokce Sevim Ozturk; Yildirim, Seniz; Simsek, Rahime; Butcher, Ray J.
    The present study reports the synthesis, structural characterization and myorelaxant activity evaluation of a series of 16 novel 4-naphthylhexahydroquinoline derivatives. The compounds were achieved by one-pot microwave-assisted method via a modified Hantzsch reaction. The structures of the compounds were confirmed by various spectral methods, such as IR, 1D and 2D NMR techniques and mass analysis. X-Ray studies of compound 10 provided further evidence for the proposed structure. To evaluate their myorelaxant activities, the E-max and pD(2) values of the compounds and nifedipine were determined on isolated rabbit gastric fundus smooth muscle strips. The obtained results indicated that the introduction of long chain alkyl groups, such as the 2-methoxyethyl or 2-(methacryloyloxy)ethyl moiety, to the ester group led to the most active compounds.