Effect of norbornene derivative in corpus cavernosum relaxation, as 5-HT1A agonist and 5-HT2A antagonist
Justo, AFO1; Campos, R1; Kiguti, LR1; Corvino, A2; Fiorino, F2; Frecentese, F2; Magli, E2; Perissutti, E2; Saccone, I2; De Nucci, G1
1: State University of Campinas, Brazil; 2: University of Naples Federico II, Italy
The aim of this study was to analyze the in vitro effects of Norbornene derivative (4-[3-[4-(o-methoxyphenyl)piperazin-1-yl]propoxy]-4-aza-tricyclo-[5.2.1.02,6]-dec-8-ene-3,5-dione; Nm), in the rat corpus cavernosum.
All animal procedures and experimental protocols were approved by the Institutional Committee for Ethics in Animal Research/University of Campinas (protocol number: 4120-1). Male Wistar rats (6 months) were killed under isoflurane anesthesia and corpus cavernosum was isolated, assembled in an organ bath and suspended to an isometric force transducer. Concentration-response curves were obtained for Phenylephrine (PHE) and 5-Hydroxytryptamine (5-HT) (0.01 to 1 mM). Concentration-response curves to Prazosin (PZS) and Norbornene derivative (0.01 and 100 µM) were also performed, the tissues were pre-contracted by PE (3 µM) or 5-HT (10 µM) and the potency (pEC50) and maxima response (Emax) values were obtained. Data are expressed as mean + SEM, N= 4 in all experiments.
The relaxation-induced by PZS and Nm showed Emax: 104.8%, pEC50: 7.25 ± 0.02 and Emax: 105.9%, pEC50: 6.60**, respectively, when pre-contracted by PHE. When pre-contracted by 5-HT, Nm showed Emax: 85.30%**, pEC50: 8.06 ± 0.11 , and PZS Emax: 65.02%; pEC50: 7.82 ± 0.09. In single concentration tissues pre-contracted by PHE, PZS proved be more effective than Nm (Emax: 108.45% and 72.18%, respectively). In tissues pre-contracted with 5-HT, Nm proved to be more efficient than PZS (Emax: 92.77% and 68.71%, respectively). Moreover, a concentration-response curve of PHE was performed in the presence of Nm 100nM (Emax: 2.02 ± 0.15mN; pEC50: 4.32±0.06) and PZS 100nM (Emax 1.95 ± 0.21mN; pEC50: 3.65 ± 0.16) and in the presence of vehicle (Emax: 3.26 ± 0.64mN; pEC50: 4.79 ± 0.17). In the presence of Nm, 5-HT concentration-response curve showed the inhibition of contraction in 100nM (Emax: 1.98 ± 0.04mN; pEC50: 4.35± 0.02) and PZS 100nM (Emax: 2.26 ± 0.32mN; pEC50: 4.29), compared to vehicle (Emax: 2.52 ± 4.24mN; pEC50: 4.24 ± 0.10).
In conclusion, the compound showed to be efficient in vitro experiments, acting in relaxation and contraction, by serotoninergic and adrenergics receptors and in vivo experiments will performed to analyze erectile activity.
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