DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



RBx 6198: a novel alpha1-adrenoceptor antagonist for the treatment of benign prostatic hyperplasia.

Author(s): Nanda K, Naruganahalli KS, Gupta S, Malhotra S, Tiwari A, Hegde LG, Jain S, Sinha N, Gupta JB, Chugh A, Anand N, Ray A

Affiliation(s): Department of Pharmacology, Ranbaxy Research Laboratories, Plot -20, Sector-18, Gurgaon, 122015, India. kamna.nanda@ranbaxy.com

Publication date & source: 2009-04-01, Eur J Pharmacol., 607(1-3):213-9. Epub 2009 Feb 23.

Publication type: Comparative Study

The present study, investigates the effect of RBx 6198, 2-{3-[4-(2-Isopropoxy-phenyl)-piperazin-1-yl]-propyl}-3a, 4, 7, 7a-tetrahydro-isoindole-1, 3,-dione, a novel alpha(1)-adrenoceptor antagonist, in both in vitro and in vivo test systems. RBx 6198 is a potent (nanomolar affinity) alpha(1A)-adrenoceptor antagonist with demonstrable uroselectivity in anaesthesized dog model. In radioligand binding studies using human recombinant receptors, RBx 6198 exhibited high selectivity (approximately 50 fold) for the alpha(1A)-adrenoceptor subtype as compared to alpha(1B)-adrenoceptor subtype. In order to assess tissue selectivity, the antagonistic effect of RBx 6198 on the phenylephrine induced contractile response of isolated rat prostate, spleen and aorta was characterized. RBx 6198 was 8 fold more potent in inhibiting phenylephrine-evoked contractions of isolated tissues compared to tamsulosin. However, the compound was non-selective for alpha(1A) vs. alpha(1D)-adrenoceptor like tamsulosin. In anaesthetized beagle dogs RBx 6198 suppressed the intraurethral pressure response to phenylephrine to a greater extent than the mean arterial pressure response thereby demonstrating uroselectivity consistent with in vitro binding and functional data. RBx 6198 was 6.4 fold more uroselective as compared to tamsulosin after i.v. route dose administration. Taken together all results from preclinical studies, it is suggested that RBx 6198 is a novel alpha(1)-adrenoceptor antagonist that exhibited improved pharmacological profile over tamsulosin in both in vitro and in vivo.

Page last updated: 2010-10-05

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017