In vitro and in vivo studies on the effects of the alpha‐adrenoceptor blocker IP/66 (1‐(2‐ethoxy‐2‐(3′ ‐pyridyl)ethyl)‐4‐(2′‐methoxy‐phenyl)piperazine) on urethral tone in rats

作者: Damiano Turini ; Paola Boni ; Francesca Perretti ; Stefano Manzini ; Gabriele Barbanti ; Carlo Alberto Maggi

AbstractIP/66 (1‐(2‐ethoxy‐2‐(3′‐pyridyl)ethyl)‐4‐(2′‐methoxy‐phenyl))piperazine is a newly synthetized and stereoselective alpha‐adrenoceptor blocking drug. This compound exhibits preferential blocking activity in postjunctional as compared to prejunctional alpha‐adrenergic responses. Furthermore, IP/66 inhibits phenylephrine‐induced motor response in human and rat prostatic tissue and phenylephrine‐, DMPP‐ and EFS‐induced motor responses in rat urethral tissues, being equieffective or even more potent than prazosin. Like prazosin, intravenous administration of IP/66, at doses at which no hypotensive effect is observed, induces a marked inhibition of phenylephrine or DMPP‐induced increase in urethral perfusion pressure, in anaesthetized pithed rats. Finally, IP/66 administration exerts beneficial effects in animals with surgically‐ or pharmacologically‐induced urethral outflow obstruction. As a whole, the pharmacodynamic profile of IP/66 is promising and this drug might be proposed for clinical setting evaluating its efficacy for the treatment of lower urinary tract dysfunctions.

1989-01-01·Journal of Chromatography B: Biomedical Sciences and Applications

Determination of the antihypertensive drug 1-[2-ethoxy-2-(3′-pyridyl)ethyl]-4-(2′-methoxyphenyl)piperazine (IP/66) in rat and human plasma by high-performance liquid chromatography and isotope dilution mass spectrometry

Article

作者: G. Bonacchi ; G. Moneti ; M. Fedi ; O. Agostini ; S. Manzini

In connection with pharmacokinetic studies on the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine (IP/66) (I), appropriate high-performance liquid chromatographic (HPLC) and gas chromatographic-mass spectrometric isotope dilution (GC-MS-ID) methods for its determination in rat and human plasma, respectively, were developed. In both techniques, deproteinized and basified plasma samples were extracted and purified by adsorption on an Extrelut-1 column, then the drug was eluted with dichloromethane. Quantitative HPLC analysis was performed on a C8 reversed-phase column. The mobile phase was phosphate buffer (0.02 M, pH 2.8)-acetonitrile (65:35), with UV detection at 208 nm. The internal standard was 1-[2-butoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine, a homologue of I. The inter-assay coefficient of variation (C.V.) was 9.9% for a drug level of 2 micrograms/ml. Quantitative GC-MS-ID analysis was performed with a DB-17 fused-silica capillary column using the selected-ion monitoring technique. The deuterated form of I, 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-2'-trideuteromethoxyphenyl)pipe razine, utilized as internal standard, was synthesized. The inter-assay C.V. was 7.36% for a drug level of 1 ng/ml.

1988-05-01·Arzneimittel-Forschung

Resolution and pharmacological properties of the enantiomers of the potent alpha-adrenoceptor antagonist 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine.

Article

作者: Manzini, S ; Bonacchi, G ; Fedi, M ; Agostini, O ; Perretti, F ; Castellucci, A ; Bacciarelli, C ; Boni, P

Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy-phenyl)piperazine have been carried out. Optical purity was assayed by high-pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine-induced pressor responses in pithed rat.

100 项与 IP-66 相关的药物交易

登录后查看更多信息