褪黑激素对青霉素所致癎样发作的预防作用(英文)

以往报道表明 ,褪黑激素 (melatonin ,MEL)对癫活动有作用 ,但结果并不一致。有实验表明MEL有抗作用 ,也有证据支持MEL有促作用。本文用海马内微量注射的方法 ,观察了MEL对青霉素所致样发作 (penicillin inducedseizures ,PIS)的影响 ,并对其与受体的可能作用作了探讨。发现 ,预先给予MEL对PIS有抑制作用 ,且该效应具有剂量依赖性。褪黑激素的作用可被Ⅰ型受体拮抗剂luzindole部分阻断 ,而Ⅱ型受体拮抗剂prazosine对此无影响。结果表明 ,MEL对PIS有预防作用 。

Method for quantification of prazosin in dog plasma and its application to pharmacokinetic study

A simple and sensitive high performance liquid chromatography method using fluorescence detection （HPLC- FLD） and a one-step single solvent extraction for the determination of prazosin（PZS） in dog plasma is developed and validated. After extraction with ether, the chromatographic separation of PZS is carried out using a reverse phase C18 column （ 150 mm ×4.6 mm, 5 μm） with a mobile phase of 30% acetonitrile and 70% acetic acid-sodium acetate buffer solution （pH = 3.6） and quantified by fluorescence detection operated with an excitation wavelength of 258 nm and an emission wavelength of 387 nm. The flow rate of the mobile phase is 1.0 mL/min and the retention time of PZS and the internal standard is found to be 4. 4 and 5. 8 rain, respectively. The calibration curve is linear within a concentration range from 1.0 to 1 000.0 ng/mL （ P 〉 0. 998）. The limit of detection is 0.4 ng/mL. The inter-day coefficient of variation （COV） of the calibration standards is below 5.0% and the mean accuracy is in the range from 92. 7% to 104. 2%. Moreover, by analyzing quality control plasma samples for three days, the results show that the method is precise and accurate, for the intra- and inter- day COV within 10% and the accuracy from 95.9% to 112.7%. The developed and validated method is successfully applied to phannacokinetic study for the preclinical evaluation of a new peroral PZS-sulfobutyl ether beta-cyclodextrin （PZS-SBE-β-CD） inclusion complex tablets （test preparation）, which demonstrates that the test preparation released PZS is conducted in a slow and controlled way, and the relative bioavailability of the test preparation is found to be 105.0%.

Prazosin:a potential new management tool for iatrogenic autonomic dysreflexia in individuals with spinal cord injury?

Spinal cord injury （SCI） is a devastating condition that not only results in a loss of motor functions but also severe autonomic dysfunctions （Krassioukov and Claydon, 2006）. Autonomic dysreflexia （AD） is a life threatening episode of tran- sient hypertension that occurs up to 30x/day （1 Ix/day on average） in those with cervical or high thoracic SCI （Hubli et al., 2015）. Most common triggers of AD are from stimuli such as a full bowel and/or bladder, or sexual arousal （Teasell et al., 2000）. Penile vibrostimulation （PVS） is a clinical pro- cedure for sperm retrieval used for the purpose of family planning or fertility assessment that unfortunately iatrogenically induces episodes of AD （Elliott, 2006）. Recently, we published a clinical trial highlighting that prazosin may be a viable option for treating AD secondary to PVS （Phillips et al., 2014）.

Primary prevention of posttraumatic stress disorder: drugs and implications

Because posttraumatic stress disorder(PTSD) is a highly debilitating condition, prevention is an important research topic. This article reviews possible prevention approaches that involve the administration of drugs before the traumatic event takes place. The considered approaches include drugs that address the sympathetic nervous system, drugs interfere with the hypothalamic-pituitary-adrenal(HPA) axis, narcotics and other psychoactive drugs, as well as modulators of protein synthesis. Furthermore, some thoughts on potential ethical implications of the use of drugs for the primary prevention of PTDS are presented. While there are many barriers to overcome in this field of study, this paper concludes with a call for additional research, as there are currently no approaches that are well-suited for regular daily use.

A Reevaluation of Prazosin Pharmacokinetics in a Two-Compartment Model, the Apparent Volume of Distribution and Comparative Simulations in the One-Compartment Model

Published clinical data of Prazosin were reevaluated pharmacokinetically using explicit solutions to drug concentration as a function of total time for IV bolus injection, intermittent intravenous infusion and oral routes of administration in an open two-compartment model. In a novel way, the apparent volume of distribution was estimated from a two-compartment model and found to be close to the total body water suggesting that Prazosin is distributed in all tissues both extracellularly and intracellularly. In addition, extracting the value of the apparent volume of distribution from a two-compartment model allowed comparative simulations in the one-compartment model. It is shown that dosage calculations of Prazosin intermittent infusion can be safely performed using the simpler one-compartment model equations. Lastly, several additional time-dependent pharmacokinetic parameters e.g., the peak time in the central and peripheral compartment and non-steady state and steady state peak concentration and AUC were determined using series equations for all three routes of administration, as a function of dose number and total time upon multiple drug administrations in the two-compartment model. It is also the first time that steady-state plasma drug concentration equations were derived in a two-compartment mammillary model.

Insights into cardio-oncology:Polypharmacology of quinazoline-based α1-adrenoceptor antagonists

New uses of cardiovascular drugs with proven experience are emerging,including for treating cancer.Quinazoline is a compound made up of two fused six member simple aromatic rings,benzene and pyrimidine rings,with several biological effects.Cardiologists first used quinazoline-based α1-adrenoceptor antagonists prazosin,doxazosin,and terazosin; currently available data support their use as safe,well tolerated,and effective add-on therapy in uncontrolled hypertension with additional favourable metabolic effects.Recent findings highlight the anticancer effects of quinazoline-based α1-adrenoceptor antagonists,indicating that they may have a significant role in uncontrolled hypertensive cancer patients without signs of ischemia.

Activity Induced by a Naphthalene-Prazosin Derivative on Ischemia/Reperfusion Injury in Rats

In this study, a new naphthalene-prazosin derivative (compound 5) was synthetized with the objective of evaluating its activity on ischemia/reperfusion injury. The Langendorff technique was used to evaluate the effect of the compound 5 on ischemia/reperfusion injury. Additionally, the mechanism of action involved in the activity exerted by the compound 5 on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in absence or presence of following compounds;prazosin, metoprolol, indomethacin and nifedipine. The results showed that the compound 5 reduced infarct size compared with the control conditions. Other results showed that the compound 5 significantly increases (p = 0.05) the perfusion pressure and coronary resistance in isolated rat heart. In addition, other data indicate that the compound 5 increases left ventricular pressure in a dose-dependent manner (0.001 to 100 nM);however, this phenomenon was significantly inhibited by nifedipine at a dose of 1 nM (p = 0.05) and this effect was independent of cAMP levels. In conclusion, these data suggest that the naphthalene-prazosin derivative exerts a cardio protective effect via the calcium channels activation and consequently induces changes in the left ventricular pressure levels. This phenomenon results in a decrease of myocardial necrosis after ischemia and reperfusion.

The Presence of Phases and the Inability of the Classical Compartment Models to Provide Pharmacokinetic Parameters of Physiological Significance for Lipophilic Drugs

The first biphasic open one-compartment pharmacokinetic model is described. Its analytical solutions to drug concentration were developed from parameters of an open two-compartment pharmacokinetic model. The model is used to explain the unusually large compartment volumes and apparent volumes of distribution of lipophilic drugs, as well as to identify which of the pharmacokinetic parameters of the classical compartment models are biologically relevant.

Effects of AR Antagonist on Myocardial α_1-AR Density and VERP-D after Myocardial Infarction

Objectives To investigate the effects of adrenergic receptor antagonist (metoprol- ol or prazosin) on myocardial α1-AR density and the changes of ventricular effective refractory period disper- sion (VERP-D) in rabbits after myocardial infarction. Methods twenty-four adult male New Zealand rab- bits were divided into four groups at random: control group ( n = 6 ) ; MI with placebo group ( n = 6 ) ; MI with metoprolol group ( n = 6) ; MI with prazosin group ( n = 6 ). The rabbits received corresponding drugs for seven days, beginning at the first day after MI with metoprolol 5 mg · kg-1 · d-1 or prazosin 0.5 mg · kg-1 · d-1. On the seventh day after MI, VERP-D and myocardial α1-AR density were measured and meanwhile, myocardial β-AR was also measured. Results In the placebo group, the density of ventricu- lar α1-AR was increased in comparison with control group (α1-AR in normal region 36. 9 ± 0. 2 vs 27. 3 ± 0. 9 fmol mg-1 pro-1 ,P <0.01; α1-AR in ischemic region 33.0±0.9 vs 26.6±0.4 fmol mg-1 pro-1 P<0.01).In the metoprolol group, it was also increased in compari- son with control group(α1-AR in normal region 44. 7 ± 1.5 vs 27.3 ±0.9 fmol mg-1 pro-1 ,P <0. 01; α1-AR in ischemic region 33. 6 ± 0. 5 vs 26. 6 ± 0. 4 fmol mg-1 pro-1 , P <0. 01 ). Meanwhile the density of ven- tricular α1-AR in normal region in the metoprolol group was increased in comparison with placebo group (44.7 ± 1.5 vs 36. 9 ±0.2 fmol mg-1 pro-1 ,P <0. 01). While it decreased in the prazosin group in comparison withcontrol group (α1 -AR in normal region 22. 5 ± 0 . 6 vs 27.3±0.9 fmol mg-1 pro-1,P<0.01; α1-AR in ische- mic region 20.9±0.4 vs 26.6 ±0.4 fmol mg-1 pro-1 , P <0.01). VERP-D was increased after MI(P <0.01). After treatment with metoprolol or prazosin, VERP-D was decreased ( P < 0. 01 ). Conclusions After a- cute MI, α1-AR of ventricular myocardium was upregu- lated, which may be accompanied by its activitation. The density of myocardial α1-AR became upregulated more dramatically treated with metoprolol and downreg- ulated with prazosin. When treated with metoprolol or prazosin, VERP-D decreased.

The fate of prazosin and levonorgestrel after electrochemical degradation process: Monitoring by-products using LC-TOF/MS

Prazosin（PRZ） and levonorgestrel（LNG） are widely used as an anti-disease drugs due to their biological activity in the human body. The frequent detection of these compounds in water samples requires alternative technologies for the removal of both compounds. After electrochemical degradation of PRZ and LNG, the parent compounds could be completely removed after treatment, but the identification and characterization of by-products are necessary as well. In this study, the effects of NaCl concentration and applied voltage were investigated during the electrochemical degradation process. The results revealed that the increase of NaCl concentration and applied voltage could promote the generation of hypochlorite OCl-and then enhance the degradation of PRZ and LNG. After initial study, 6 V and 0.2 g NaCl were selected for further experiments（96% and 99% removal of PRZ and LNG after 40 min, respectively）. Energy consumption was also evaluated and calculated for PRZ and LNG at 3, 6 and 8 V. Solid phase extraction（SPE） method plays an important role in enhancing the detection limit of by-products. Furthermore, characterization and identification of chlorinated and non-chlorinated by-products were conducted using an accurate liquid chromatography-time of flight/mass spectrometry LC-TOF/MS instrument. The monitoring of products during the electrochemical degradation process was performed at6 V and 0.2 g NaCl in a 50 m L solution. The results indicated that two chlorinated products were formed during the electrochemical process. The toxicity of by-products toward E. coli bacteria was investigated at 37°C and 20 hr incubation time.