Comparative Biodistribution and Pharmacokinetic Analysis of Cyclosporine-A in the Brain upon Intranasal or Intravenous Administration in an Oil-in-Water Nanoemulsion Formulation

2015 ◽  
Vol 12 (5) ◽  
pp. 1523-1533 ◽  
Author(s):  
Sunita Yadav ◽  
Florence Gattacceca ◽  
Riccardo Panicucci ◽  
Mansoor M. Amiji
Keyword(s):  
Intravenous Administration ◽  
Cyclosporine A ◽  
Pharmacokinetic Analysis ◽  
Oil In Water ◽  
The Brain

Effect of stimulation of nucleus raphe dorsalis on carotid blood flow. II. The cat

1985 ◽  
Vol 248 (2) ◽  
pp. R263-R269 ◽  
Author(s):  
P. J. Goadsby ◽  
R. D. Piper ◽  
G. A. Lambert ◽  
J. W. Lance
Keyword(s):  
Intravenous Administration ◽  
Spinal Cord Section ◽  
Homocysteic Acid ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Blocker ◽  
Raphe Dorsalis ◽  
Constrictor Response ◽  
The Brain ◽  
Stimulation Of

The dorsal raphe nucleus (DRN) and surrounding midbrain of 74 cats were stimulated both electrically and chemically, and carotid flows were measured with electromagnetic flow probes. Stimulation of the DRN caused a frequency-dependent decrease in common carotid vascular resistance, which was abolished by bilateral section of the facial nerve intracranially. Injection of DL-homocysteic acid into the DRN reproduced the effect of electrical stimulation, indicating that the responses arose from excitation of cell bodies within the DRN, not from fibers of passage. The responses were mediated entirely within the brain stem since they remained intact after high spinal cord section. The vasodilator response was blocked by the intravenous administration of the nicotinic ganglion blocker hexamethonium but not by the alpha-adrenoceptor blocker phentolamine. The responses were unaffected by intravenous administration of methysergide but were markedly reduced after depletion of central serotonin by pretreatment with the serotonin depletor, p-chlorophenylalanine. A poststimulus constrictor response was mediated by release of catecholamines from the adrenal medulla and was blocked by the alpha-adrenoceptor antagonist phentolamine. No response involved supracollicular mechanisms since they persisted after decerebration.

scholarly journals STUDIES IN THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION

1960 ◽  
Vol 111 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Abraham Penner ◽  
Alice Ida Bernheim
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Intravenous Administration ◽  
Shiga Toxin ◽  
Third Ventricle ◽  
Dosage Level ◽  
Ventricular System ◽  
The Third ◽  
The Central Nervous System ◽  
The Brain

The introduction of Shiga toxin into the ventricular system of the brain with major location in the third ventricle resulted in a response similar to that following the administration of the toxin either intravenously or by cross-circulation. The intravenous administration at the dosage level employed would have elicited no response. These observations lend support to the hypothesis that Shiga toxin activates some mechanisms in the central nervous system which are capable of producing visceral lesions. These mechanisms are those which control the vasomotor components of homeostasis. This hypothesis permits an explanation of the proximo-distal and intramural features of the lesion.

scholarly journals Analgesic Efficacy and Safety of DALDA Peptide Analog Delivery to the Brain Using Oil-in-Water Nanoemulsion Formulation

2014 ◽  
Vol 31 (10) ◽  
pp. 2724-2734 ◽  
Author(s):  
Lipa Shah ◽  
Praveen Kulkarni ◽  
Craig Ferris ◽  
Mansoor M. Amiji
Keyword(s):  
Analgesic Efficacy ◽  
Efficacy And Safety ◽  
Peptide Analog ◽  
Oil In Water ◽  
The Brain

The Distribution of Morphine in the Brain in Fatal Cases Due to the Intravenous Administration of Heroin

1978 ◽  
Vol 2 (2) ◽  
pp. 62-67 ◽  
Author(s):  
V.R. Spiehler ◽  
R.H. Cravey ◽  
R.G. Richards ◽  
H.W. Elliott
Keyword(s):  
Intravenous Administration ◽  
The Brain

scholarly journals Functional activity of p-glycoprotein in blood-brain barrier during experimental par-kinson's syndrome

2019 ◽  
Vol 27 (2) ◽  
pp. 150-159
Author(s):  
Ivan V. Chernykh ◽  
Aleksey V. Shchulkin ◽  
Pavel Yu. Mylnikov ◽  
Maria V. Gatsanoga ◽  
Maria M. Gradinar ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Intravenous Administration ◽  
Functional Activity ◽  
Brain Barrier ◽  
Renal Tubules ◽  
Parkinson's Syndrome ◽  
Parkinson’S Syndrome ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Background. P-glycoprotein (Pgp, ABCB1-protein) is a membrane transporter with broad substrate specificity that is localized in hepatocytes, enterocytes, epithelial renal tubules, and also in tissue barriers, including blood-brain barrier (BBB). Increased Pgp activity in BBB is one of the reasons for the pharmacoresistance of a number of CNS diseases. Aim. Analysis of Pgp functional activity in BBB during experimental Parkinson's syndrome. Materials and Methods. The work was performed on 90 Wistar rats, divided into 3 series (n=30 in each). The 1 series (control) was subcutaneously injected sunflower oil once a day for 7 days, and Pgp activity in BBB was assessed on the 8th day. The 2 and 3 series (pathology control) - were administered rotenone at a dose of 2.5 mg/kg once a day for 7 and 28 days respectively to simulate parkin-sonism. At the end of the experiment Pgp activity was estimated. To confirm Parkinson's syndrome, in addition to the clinical picture, level of dopamine in midbrain and striatum was determined using enzyme-linked immunosorbent assay. Pgp functional activity in BBB was assessed by the degree of penetration of its marker substrate fexofenadine into the brain after its intravenous administration at a dose of 10 mg/kg. The content of fexofenadine in the blood plasma and in brain tissue was estimated by the area under pharmacokinetic curve of the substance (in the blood or brain tissues) - AUC0-t(plasma) or AUC0-t(brain) respectively. To assess the BBB permeability the ratio AUC0-t(brain) / AUC0-t(plasma) was calculated. Results. Rotenone administration led to the development of parkinsonism typical picture: muscle stiffness, hypokinesia, gait instability. There was a decrease in dopamine level in the striatum after 7 days by 69.6% (p=0.095), after 28 days - by 93.9% (p=0.008), in midbrain - by 72.7% (p=0.095) and 68.7% (p=0.032) respectively. Fexofenadine AUC0-t(plasma) and AUC0-t(brain) after its intravenous administration to control rats were 266.2 (246.4; 285.6) μg/ml*min and 5.9 (5.8;6.6) µg/g*min respectively, AUC0-t(brain) /AUC0-t(plasma) - 0.020 (0.019; 0.022). When rotenone was for 7 days administered - fexofenadine AUC0-t(brain) increased 2.02 times (p=0.0163), AUC0-t(brain) / AUC0-t(plasma) - 2.4 times (p=0.0283). 28 days administration of rotenone led to augmentation of AUC0-t(brain) of fexofenadine by 1.75 times (p=0.0283), AUC0-t(brain) / AUC0-t(plasma) - by 2.27 times (p=0.0163). Conclusions. The development of Parkinson’s syndrome, caused by the administration of rotenone, inhibits Pgp functional activity in BBB, which is confirmed by the accumulation in the brain marker substrate of the transporter - fexofenadine.

scholarly journals Development and Validation of a UPLC-MS/MS Method for the Quantitative Determination and Pharmacokinetic Analysis of Cirsimarin in Rat Plasma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
En Zhang ◽  
Ying Wang ◽  
Fuyi Xie ◽  
Xinlei Zhuang ◽  
Xianqin Wang ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
High Performance ◽  
Rat Plasma ◽  
Biological Properties ◽  
Pharmacokinetic Analysis ◽  
Standard Curve ◽  
The Matrix ◽  
Liquid Chromatography Tandem Mass ◽  
Development And Validation

Cirsimarin is a bioactive antilipogenic flavonoid isolated from the cotyledons of Abrus precatorius and represents one of the most abundant flavonoids present in this plant species. Cirsimarin exhibits excellent antioxidant, lipolysis, and other biological properties; it can effectively trigger lipid movement and demonstrates antiobesity effects. In this work, an ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of cirsimarin in rat plasma after intravenous administration. A standard curve of cirsimarin in blank rat plasma was generated over the concentration range of 1–3000 ng/mL. Six rats were administered cirsimarin intravenously (1 mg/kg). The method only required 50 μL of plasma for sample preparation, and the plasma proteins were precipitated with acetonitrile to pretreat the plasma sample. The precisions of cirsimarin in rat plasma were less than 14%, while the accuracies varied between 92.5% and 107.3%. In addition, the matrix effect varied between 103.6% and 107.4%, while the recoveries were greater than 84.2%. This UPLC-MS/MS method was then applied in measuring the pharmacokinetics of cirsimarin in rats. The AUC(0-t) values of cirsimarin from the pharmacokinetic analysis were 1068.2 ± 359.2  ng/mL·h for intravenous administration. The half-life ( t 1 / 2 ) was 1.1 ± 0.4  h (intravenous), indicating that the metabolism of the compound was quick in the rats. Exploring the pharmacokinetics of cirsimarin in vivo can help better understand its metabolism.

scholarly journals Accumulation and Removal of Hg203 in Different Regions of the Rat Brain

1978 ◽  
Vol 5 (4) ◽  
pp. 397-400 ◽  
Author(s):  
R.F. Butterworth ◽  
M. Gonce ◽  
A. Barbeau
Keyword(s):  
Rat Brain ◽  
Medulla Oblongata ◽  
Intravenous Administration ◽  
Methyl Mercury ◽  
Regional Distribution ◽  
Early Peak ◽  
The Brain

SUMMARY:We have studied the brain regional distribution of methyl mercury following intravenous administration of CH3203HgCl in rat. Early peak levels were obtained in cerebellum, medulla oblongata and midbrain. The efficacy of removal of 203Hg by different chelators is also region dependent. The most efficient chelator for brain mercury proved to be mesodimercaptosuccinic acid.

scholarly journals Brain Targeting of anti-HIV Nucleosides: in vitro and in vivo Evaluation of 6-chloro-2′,3′-dideoxypurine, a Lipophilic Prodrug of 2′,3′-dideoxyinosine

1994 ◽  
Vol 5 (5) ◽  
pp. 304-311 ◽  
Author(s):  
K. J. Doshi ◽  
F. D. Boudinot ◽  
J. M. Gallo ◽  
R. F. Schinazi ◽  
C. K. Chu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Oral Administration ◽  
Intravenous Administration ◽  
Brain Targeting ◽  
The Central Nervous System ◽  
Intravenous And Oral Administration ◽  
The Brain

Lipophilic 6-halo-2′,3′-dideoxypurine nucleosides may be useful prodrugs for the targeting of 2′,3′-dideoxyinosine (ddl) to the central nervous system. The purpose of this study was to evaluate the potential effectiveness of 6-chloro-2′,3′-dideoxypurine (6-CI-ddP) for the targeting of ddl to the brain. In vitro studies indicated that the adenosine deaminase-mediated biotransformation of 6-CI-ddP to ddl was more rapid in mouse brain homogenate than in mouse serum. The brain distribution of 6-CI-ddP and ddl was assessed in vivo in mice following intravenous and oral administration of the prodrug or parent drug. Brain concentrations of ddl were similar after intravenous administration of 6-CI-ddP or ddl. However, after oral administration of the 6-CI-ddP prodrug, significantly greater concentrations of ddl were seen in the brain compared to those found after oral administration of ddl. The brain:serum AUG ratio (expressed as a percentage) of ddl after intravenous administration of 50 mg kg−1 of the active nucleoside was 3%. Following oral administration of 250 mg kg−1 ddl, low concentrations of ddl were detected in the brain. Brain:serum AUC ratios following intravenous and oral administration of the prodrug 6-CI-ddP were 19–25%. Thus, brain:serum AUC ratios were 6- to 8-fold higher after prodrug administration than those obtained after administration of the parent nucleoside. Oral administration of 6-CI-ddP yielded concentrations of ddl in the brain similar to those obtained following intravenous administration. The results of this study provide further evidence that 6-CI-ddP may be a useful prodrug for delivering ddl to the central nervous system, particularly after oral administration.

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