Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ejphar.2006.05.005
Title: Mechanisms of direct relaxant effect of sildenafil, tadalafil and vardenafil on corpus cavernosum
Authors: Lau, L.-C. 
Adaikan, P.G. 
Keywords: Corpus cavernosum
Signal transduction
Sildenafil
Tadalafil
Vardenafil
Issue Date: 2006
Source: Lau, L.-C., Adaikan, P.G. (2006). Mechanisms of direct relaxant effect of sildenafil, tadalafil and vardenafil on corpus cavernosum. European Journal of Pharmacology 541 (3) : 184-190. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ejphar.2006.05.005
Abstract: Sildenafil, tadalafil, vardenafil and verapamil induced concentration-dependent relaxation of the rabbit corpus cavernosum muscle precontracted with noradrenaline. The maximal relaxation (%) at 20 μM was 61.4 ± 6.9, 32.4 ± 5.4, 100.0 ± 5.5 and 86.6 ± 5.1 (n = 5 each) respectively. Pre-incubation of cavernosal muscle strips with Nω-nitro-l-arginine or guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) but not adenylate cyclase inhibitor, cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine] (MDL12330A) culminated in only a 20-30% reduction in muscle relaxant action of the 3 phosphodiesterase inhibitors. This suggests that another mechanism of relaxation independent of nitric oxide-cGMP or cAMP pathway was involved. Higher concentrations of sildenafil (100 μM) and vardenafil (10 and 100 μM) produced non-competitive antagonism of noradrenaline-induced contraction characterized by reduced maximal effect. In contrast, tadalafil was devoid of significant effect on noradrenaline. On K+-depolarized tissues, sildenafil was as potent as vardenafil whereas tadalafil was the least effective in relaxing K+-induced tone. The maximal relaxation (% of K+-induced tone) at 20 μM sildenafil, tadalafil and vardenafil was respectively 84.1 ± 6.5, 9.0 ± 19.9, and 88.9 ± 6.2 (n = 5 each). In addition, verapamil, sildenafil and vardenafil were more efficacious than tadalafil in reversing tonic contractions by Ca2+ channel activator, 1,4,dihydro-2,6-dimethyl-5-nitro-4-[2(triflouromethyl)phenyl]pyridine-3-carboxylic acid methyl ester (BAY K-8644). These results indicate that vardenafil and sildenafil possess direct muscle relaxant potential possibly via inhibiting Ca2+ influx through both receptor-operated and voltage-dependent Ca2+ channels whereas tadalafil appears capable of inhibiting receptor-operated transmembrane Ca2+ entry only. © 2006 Elsevier B.V. All rights reserved.
Source Title: European Journal of Pharmacology
URI: http://scholarbank.nus.edu.sg/handle/10635/25980
ISSN: 00142999
DOI: 10.1016/j.ejphar.2006.05.005
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

28
checked on Dec 7, 2017

WEB OF SCIENCETM
Citations

24
checked on Nov 29, 2017

Page view(s)

122
checked on Dec 11, 2017

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.