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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-[,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.


Work supported by industry: no.

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