• Biomolecules & Therapeutics
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• v.13 no.2
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• pp.90-94
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• 2005

Prazosin hydrochloride is an antihypertensive drug with selective ${\alpha}_1$-adrenoreceptor blocking effects. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of prazosin in human plasma. A reversed-phase C18 column was used for the separation of prazosin and terazosin (internal standard) with a mobile phase composed of water, acetonitrile and triethylamine(75:25:0.1, V/V;pH5.0) at a flow rate of 1.5 ml/min. the fluorescence detector was set at excitation and emissionwavelengths of 250 and 370 nm, respectively. Intra-and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 0.5 ng/ml. Good recovery (>80%) was seen in plasma. Prazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of a single 2-mg dose as prazosin base to 16 healthy volunteers. The maximum plasma concentration of prazosin was 23.1 ${\pm}$ 16.5 ng/ml at 2.1 h, and the mean area under the curve and elimination half-life were calculated to be 108.4 ${\pm}$ 74.2 ng ${\cdot}$hr/ml and 2.5 ${\pm}$ 0.6 h, respectively.

• Journal of Convergence for Information Technology
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• v.12 no.4
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• pp.119-125
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• 2022

In the study, we endeavored to investigate the effect of phenylephrine, isoprenaline and prazosin on the tissue-specific vascular contractility and to determine the mechanism involved. There were few reports addressing the question whether thin or thick filament modulation is included in phenylephrine, isoprenaline and prazosin-induced regulation. We hypothesized that isoprenaline and prazosin play a role in tissue-dependent regulation of vascular contractility. Denuded arterial muscles of Sprague-Dawley male rats were suspended in organ baths and isometric tensions were transduced and recorded using isometric transducers and an automatic data acquisition system. Interestingly, sustained continuous contraction of thoracic and abdominal aorta. Furthermore, isoprenaline and prazosin together with phenylephrine inhibited transiently and persistently vasoconstriction of thoracic and abdominal aorta suggesting that additional mechanisms (e.g. decreased receptor density, chemical interaction, postreceptor signaling or distribution of agonists) might be included in the modulation of vascular contractility.

• Journal of Pharmaceutical Investigation
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• v.13 no.4
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• pp.173-182
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• 1983

The influence of prazosin (0.1 mg/kg i.v.) on the excretion and diuretic action of furosemide (2mg/kg i.v.) in rabbits was studied to investigate an interaction between ${\alpha}-adrenergic$ blocking agent, prazosin and furosemide. The results were as follows; 1) With the combined administration of prazosin and furosemide, the plasma concentration of furosemide was increased, the urinary excretion rate and renal clearance of furosemide were reduced, and tile biological half-life of furosemide was increased. 2) The diuretic action of furosemide was significantly reduced with the combined administration of prazosin: maximal decrease in urine volume, urinary electrolytes, clearance of $Na^+$ and $Cl^-$, and GFR and RPF, as well as maximal increase in $Na^+$ reabsorption rate were noted 10 minutes after administration of furosemide (2mg/kg i.v.)

• YAKHAK HOEJI
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• v.32 no.2
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• pp.129-136
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• 1988

Effects of the selective alpha-adrenoceptor agonists, clonidine, oxymetazoline and phenylephrine, on heart rate and contractile force were investigated in the isolated frog atria and it was attempted to examine the influence of adrenoceptor antagonist upon those. Clonidine produced dose-dependent negative chronotropic and positive inotropic effects. The negative chronotropic effect was significantly attenuated in the presence of prazosin and yohimbine but not propranolol. The positive inotropic effect was significantly attenuated by prazosin, yohimbine and propranolol. Oxymetazoline produced dose-dependent negative chronotropic and inotropic effects. The negative chronotropic effect was significantly attenuated in the presence of prazosin, which was partially augmented by yohimbine but was not affected by propranolol. The negative inotropic effect was not affected by propranolol but it was partially augmented by yohimbine and was partially attenuated by prazosin. Phenylephrine produced dose-dependent positive chronotropic and inotropic effects. The positive chronotropic and inotropic effect were significantly attenuated in the presence of propranolol but were not affected by prazosin and yohimbine. These results suggest that the negative chronotropic effect by clonidine and oxymetazoline is mediated by alpha-adrenoceptors, the positive chronotropic and inotropic effects by phenylephrine are mediated by beta-adrenoceptors, and alpha-adrenoceptors mediated the inhibitory chronotropic responses exists in the isolated frog atria.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.416-426
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• 1991

The effects of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin) on $\alpha_1$-adrenoceptor-mediated vasoconstrictions were studied in the endothelium-denuded rat aorta. In these experiments, the mobilization of intracelluier calcium and translocation of extracellular calcium were also studied. To exclude the modulation of endothelium releasing EDRF and EDCF, the endothelium was removed in all rat aortas. Contraction induced by phenylephrine (a full $\alpha_1$-adrenoceptor agonist) was separated into a fast phasic component of the response due to the release of intracellular calcium and a slow tonic one due to the influx of extracellular calcium. Pretreatments with increasing doses of reversible $\alpha_1$-adrenoceptor antagonist prazosin, as well as irreversible $\alpha_1$-adrenoceptor antagonist dibenamine, inhibited the phasic component of phenylephrine-induced contraction more effectively than the tonic one. Pretreatment of dibenamine (0.2 $\mu{M}$) or prazosin (10 nM) to the rat aorta abolished phasic response but remained tonic one about 41% and 51%, respectively. These results suggest that as the efficiency of phenylephrine was progressively reduced by pretreatments with increasing doses of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin), the contraction induced by phenylephrine became progressively more dependent on the influx of extracellular calcium.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.67-74
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• 1989

The effect of guanabenz on volume-induced micturition reflex contraction (VIMRC) in urethane-anethetized female rats was examined under adrenalectomy, chemical-sympathectomy, ganglionectomy, alpha-1, or alpha-2 blockade. Intracerbroventricular administration of guanalberz had little effect on VIMRC, but topical application suppressed amplitude and frequency of VIMRC. Guanabenz intravenous injection dose-dependently suppressed amplitude and frequency of VIMRC, with complete inhibition at dose of $100\;{\mu}g/kg$, but phenylephrine had no effect on VIMRC. Intravesicular peak pressure and amplitude of VIMRC were increased by 6-hydroxydopamine (6-OHDA) treatment when compared with control value, but yohimbine-, prazosin-hexamethonium-treatment and adrenalectomy did not show changes in VIMRC. Dose-response curve of guanabenz on amplitude and frequency of VIMRC shifted significantly to the right by treatment of yohimbine and 6-OHDA, and adrenalectomy. Median inhibitory dose $({\mu}g/kg)$ of guanabenz to amplitude of VIMRC showed 27.3 in control group, 381.6 in yohimbine, 294.1 in 6-OHDA and 54.1 in hexamethonium, and 38.8 in prazosin. Those of guanabenz to frequency of VIMRC showed 41.7 in control group, 571.1 in yohimbine, 410.8 in 6-OHDA, 141.4 in adrenalectomy, 59.6 in hexamethoinum and 31.4 in prazosin. These results suggest that guanabenz inhibits VIMRC through alpha-2 receptor stimulation rather than alpha-1 receptor stimulation and that catecholiamines released from sympathetic nerve ending and adrenal gland play a role in the inhibition.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.59-67
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• 1982

1) Oxymetazoline, which has been known as an agonist for${\alpha}_1-adrenoceptor$ in various peripheral tissues, caused a pressor response in urethane-anesthetized rabbits when given intra-ventricularly. This pressor response was little affected by pretreatment of rabbits with i.v. guanethidine or chlorisondamine, but it was weakened in rabbits pretreated with either of i.v. phentolamine or guanethidine and chlorisondamine and in guanethidine-pretreated adrenal-ligated rabbits. 2) The pressor to intraventricular oxymetazoline was markedly attenuated by intraventricular pretreatment with prazosin, whereas intraventricular pretreatment with yohimbine or piperoxan did not affect this response. 3) Reserpine-pretreated rabbits also responded with hypertension to intraventricular oxymetazoline, which was markedly diminished by pretreatment with intraventricular prazosin but not affected by yohimbine. 4) Oxymetazoline, given intravenously, produced a pressor response in both whole and spinal rabbits. Intravenous prazosin, phentolamine and yohimbine, in this order, showed greater antagonizing effect to this pressor response. 5) The results indicate that oxymetazoline acts an agonist for ${\alpha}_1-adrenoceptors$ in the rabbit brain participating in the regulation of the blood pressure and in the vasculature of rabbits.

• YAKHAK HOEJI
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• v.30 no.3
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• pp.157-162
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• 1986

$\alpha$-Adrenoceptor subtypes in the isolated rat aortic strips were examined by using agonists and antagonists which have varying selectivity for $\alpha_1$- and $\alpha_2$- adrenoceptors. Norepinephrine and phenylephrine produced a similar magnitude of maximum contractions. $pA_2$ values for prazosin and yohimbine were not significantly different using norepinephrine or phenylephrine as the agonist, suggesting a single population of alpha-adrenoceptor. Contractile responses produced by alpha-agonists were antagonized more effectively by prazosin (approximately 1000 fold) than by yohimbine.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.101-111
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• 1990

The effect of physostigmine (PS), which has been shown to act on the muscarinic receptors in the brains of the rat, dog and cat, on the arterial blood pressure (BP) was investigated in urethane-anesthetized rabbits. Intravenous (iv) PS, $25{\sim}300\;{\mu}g/kg$, caused little change in BP. However, after treatment of rabbits with either of chlorisondamine (CS), hexamethonium, intracerebroventricular (icv) clonidine, icv xylazine and icy reserpine iv PS produced a pressor response. Spinalization of the rabbit also caused iv PS to increase BP. The pressor effect of iv PS in CS-treated rabbits was markedly reduced after prazosin or pirenzepine. Iv PS inhibited the pressor response to McN-A-343 in CS-treated and in spinal rabbits; alternately during the infusion of McN-A-343 iv PS failed to produce the pressor response. The pressor response to DMPP was not affected by iv PS. Icv PS, $12{\sim}200\;{\mu}g/kg$, produced a pressor response which was accentuated after CS-treatment. This pressor effect was inhibited, though not complete, by prazosin or by pirenzepine. A simultaneous treatment of rabbits with both $[Sar^{1},\;Ala^{8}]-angiotensin$ II, an angiotensin II antagonist, and prazosin or pirenzepine almost completely abolished the pressor effect of icv PS, whereas the angiotensin II antagonist did not enhance the inhibitory effect of pirenzepine and prazosin on the pressor response to iv PS . Icv pirenzepine blocked the pressor response to icv PS without affecting that to iv PS. The present results show that the pressor response to iv PS in CS-treated and in spinal rabbits arises from stimulation of the muscarinic receptors in the sympathetic ganglia, whereas the pressor response by icv PS via activation of the muscarinic receptors in the brain which causes an enhancement in the outflow of sympathetic discharge and angiotensin. The results also suggest that iv PS is unable to produce a pressor response in the rabbit unless the sensitivity of the gangionic muscarinic receptors is altered by ganglionic nicotinic blockade, by the decrease of central sympathetic outflow on the sympathetic ganglia or by spinalization.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.105-105
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• 2003

A rapid and reproducible high performance liquid chromatographic assay of prazosin in human plasma was developed. After addition of internal standard (IS, terazosin hydrochloride) and alkalization of the plasma, the drug and IS were extracted into t-butylmethylether. The organic phase was back-extracted into 0.05% phosphoric acid and 50 ${\mu}\ell$ of the acid solution was injected into a reverse-phase C18 column with a mobile phase consisting of water : acetonitrile : triethylamine = 75 : 25 : 0.1 (pH 5.0). The samples were detected utilizing a fluorescence detector. A