scholarly journals The Dipeptides Ile-Tyr and Ser-Tyr Exert Distinct Effects on Catecholamine Metabolism in the Mouse Brainstem

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Kazuki Moriyasu ◽  
Takashi Ichinose ◽  
Akane Nakahata ◽  
Mitsuru Tanaka ◽  
Toshiro Matsui ◽  
...  
Keyword(s):  
Oral Administration ◽  
Homovanillic Acid ◽  
The Body ◽  
Dopamine Turnover ◽  
Catecholamine Metabolism ◽  
Noradrenaline Turnover ◽  
Catecholamine Synthesis ◽  
Dopamine Metabolites ◽  
Dihydroxyphenylacetic Acid ◽  
The Brain

Catecholamine synthesis and transmission in the brain are influenced by the availability of Tyr in the body. In this study, we compared the effects of oral administration of Tyr-containing dipeptides Ile-Tyr, Ser-Tyr, and Tyr-Pro with Tyr alone on catecholamine metabolism in the mouse brainstem. Among these dipeptides, Ile-Tyr administration led to increases in dopamine, the dopamine metabolites homovanillic acid, and 3,4-dihydroxyphenylacetic acid, compared to administration of Ser-Tyr, Tyr-Pro, or Tyr alone. In comparison, administration of Ser-Tyr induced significantly increasing noradrenaline turnover, while Tyr-Pro administration suppressed dopamine turnover. Therefore, oral administration of Ile-Tyr, Ser-Tyr, and Tyr-Pro differentially affected metabolism of dopamine and noradrenaline. These observations strongly suggest that Tyr-containing dipeptides exert distinct effects on catecholamine metabolism in the brainstem when ingested orally.

scholarly journals Development of a physiologically based pharmacokinetic (PBPK) model of psilocybin and psilocin from magic mushroom in rats and humans

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 209
Author(s):  
Prinya Musikaphongsakul ◽  
Kimheang Ya ◽  
Pakpoom Subsoontorn ◽  
Manupat Lohitnavy
Keyword(s):  
Oral Administration ◽  
Pbpk Model ◽  
Simulated Data ◽  
The Body ◽  
Time Profiles ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based ◽  
Intravenous And Oral Administration ◽  
The Brain ◽  
Good Agreement

Background: Psilocybin (PB) is a psychoactive compound commonly found in magic mushroom (Psilocybe cubensis). PB is quickly converted by the body to psilocin (PI), which has a psychedelic effect through the activation of the 5-HT2A receptor in the brain. The objective of this study is to develop a physiologically based pharmacokinetic (PBPK) model of PB and PI in rats and humans for predicting concentrations of the psychoactive substance in the brain. Methods: Following a search in PubMed, three studies were retrieved and information concerning concentration-time profiles of PI were extracted from the selected studies. In the study in rats, PI was orally administered with a dose of 10.1 mg/kg. There were two studies in humans following a single intravenous dose of PB (1 mg) and oral dose of PB (0.224 mg/kg and 0.3 mg/kg). Berkeley Madonna software was used for computer coding and simulations. The developed PBPK model consisted of seven organ compartments (i.e. lung, heart, brain, fat, muscle, kidney, and liver). Results: The simulations show a good agreement between observed and simulated data, although results for oral administration in rats and humans showed under-predictions and results for intravenous administration in humans showed over-predictions. Conclusions: A PBPK model of PB and PI in rats and humans was developed and could predict concentration-time profiles of PI in plasma, particularly in the brain, following intravenous and oral administration of PB. This model may be useful for a safer dosage regimen of PB for patients with some disorders.

scholarly journals Evidence on Integrating Pharmacokinetics to Find Truly Therapeutic Agent for Alzheimer’s Disease: Comparative Pharmacokinetics and Disposition Kinetics Profiles of Stereoisomers Isorhynchophylline and Rhynchophylline in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chunyuan Zhang ◽  
Xu Wu ◽  
Yanfang Xian ◽  
Lin Zhu ◽  
Ge Lin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oral Administration ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Systemic Exposure ◽  
The Body ◽  
Chinese Medicinal Herb ◽  
Disposition Kinetics ◽  
The Brain

Isorhynchophylline (IRN) and rhynchophylline (RN), a pair of stereoisomers, are tetracyclic oxindole alkaloids isolated from Uncaria rhynchophylla, a commonly used Chinese medicinal herb. These two compounds have drawn extensive attention due to their potent neuroprotective effects with promising therapeutic potential for the treatment of Alzheimer’s disease (AD). However, IRN and RN can interconvert into each other in vivo after oral administration. The present study aimed to elucidate the pharmacokinetic profiles and disposition kinetics of the administered and generated stereoisomers in the brain and cerebrospinal fluid (CSF) after oral administration of equal dose of IRN or RN to rats. Our study demonstrated that after oral administration, RN showed significantly higher systemic exposure (6.5 folds of IRN, p < 0.001) and disposition in the brain (2.5 folds of IRN, p < 0.01) and CSF (3 folds of IRN, p < 0.001) than IRN. The results indicated that interconversion between IRN and RN occurred. Notably, regardless of the orally administered IRN or RN, RN would always be one of the major or predominant forms present in the body. Our results provided sound evidence supporting further development of RN as a potential therapeutic agent for the treatment of AD. Moreover, the present study sets a solid example that integrating pharmacokinetics is crucial to identify the truly therapeutic agent.

Monoamine concentrations in cerebrospinal fluid of fetal and newborn sheep

1994 ◽  
Vol 266 (2) ◽  
pp. R472-R480 ◽  
Author(s):  
S. A. Joseph ◽  
D. W. Walker
Keyword(s):  
Cerebrospinal Fluid ◽  
Prostaglandin E2 ◽  
Gestational Age ◽  
Intravenous Infusion ◽  
Homovanillic Acid ◽  
Prostaglandin Synthesis ◽  
Fetal Hypoxia ◽  
Fetal Sheep ◽  
Dihydroxyphenylacetic Acid ◽  
The Brain

Monoamine concentrations were measured in cisternal cerebrospinal fluid (CSF) of unanesthetized fetal (115-135 days gestation) and newborn (2-34 days old) sheep. Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations decreased with gestational age; NE CSF concentrations were significantly higher in the newborn (336.4 +/- 61.7 pg/ml; n = 5) compared with the 131- to 135-day-gestation fetuses (104.0 +/- 46.3 pg/ml, n = 3; P < 0.05). Dopamine (DO), homovanillic acid (HVA), and serotonin (5-HT) concentrations in fetal CSF did not change with gestational age, and epinephrine (Epi) was undetectable in most fetal and newborn samples. Hypoxia, induced by giving the ewe 9% O2 in N2 to breathe for 30 min, resulted in a 10.78 +/- 3.94-fold (n = 5) increase of NE concentration in fetal CSF (P < 0.05); DO and DOPAC concentrations did not change. Hypoxia did not increase NE concentrations in CSF of newborn lambs. Inhibition of prostaglandin (PG) synthesis by intravenous infusion of indomethacin significantly reduced plasma prostaglandin E2 concentrations from 7.8 +/- 1.0 (n = 6) to 2.5 +/- 0.2 nmol/l (n = 3; P < 0.05), and was associated with an increase of CSF DOPAC concentrations from 2,156.3 +/- 504.5 (n = 9) to 5,453.6 +/- 1,091.3 pg/ml (n = 5; P < 0.05); NE and DO concentrations did not change significantly. These results show that catecholamines and indoleamines are released in the brain and enter the CSF of fetal sheep from at least 115 days gestation. The data also show that concentrations of some monoamines in CSF are changed by fetal hypoxia or prostaglandin synthesis.

HOMOVANILLIC ACID AND DIHYDROXYPHENYLACETIC ACID IN THE STRIATUM OF MONKEYS WITH BRAIN LESIONS

1967 ◽  
Vol 45 (1) ◽  
pp. 57-62 ◽  
Author(s):  
D. F. Sharman ◽  
L. J. Poirier ◽  
G. F. Murphy ◽  
T. L. Sourkes
Keyword(s):  
Chemical Analysis ◽  
Homovanillic Acid ◽  
Brain Lesions ◽  
Intact Side ◽  
Dihydroxyphenylacetic Acid ◽  
Macaca Mulatto ◽  
Left And Right ◽  
The Right ◽  
Derivatives Of ◽  
The Brain

Lesions were placed in the left ventromedial tegmental area of the brains of nine monkeys (Macaca mulatto). After 1–4 months, the brains were removed, and the striatum was dissected and prepared for chemical analysis. In seven animals in which the lesion was strictly unilateral, the striatal dopamine was very much reduced below the level found on the intact side of the brain. In the two monkeys in which the lesion impinged on the right side of the brain, the concentration of dopamine was reduced on both sides. Homovanillic acid and 3,4-dihydroxyphenylacetic acid, metabolic derivatives of dopamine, were measured in the left and right striata of four and five monkeys respectively. Both compounds were present at subnormal concentrations on the side of the lesion. The concentration of homovanillic acid did not fall to as great an extent as did that of dopamine. These results are discussed in relation to data reported by others in regard to (a) animals treated with tranquilizing drugs, and (b) brains of patients who died with Parkinson's disease.

Polychlorinated biphenyl induced hepatocyte alterations

1987 ◽  
Vol 45 ◽  
pp. 716-717
Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal
Keyword(s):  
Lipid Droplets ◽  
Wistar Rats ◽  
Homovanillic Acid ◽  
Polychlorinated Biphenyl ◽  
Corn Oil ◽  
Environmental Pollutants ◽  
Short Term ◽  
Pcb Congeners ◽  
Urinary Levels ◽  
The Brain

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).

EXPERIMENTAL ASSESSMENT OF THE NANOPARTICLES TOXICITY OF NICKEL OXIDE IN TWO SIZES IN THE SUBCHRONIC EXPERIMENT

2018 ◽  
pp. 30-35
Author(s):  
M.P. Sutunkova ◽  
B.A. Katsnelson ◽  
L.I. Privalova ◽  
S.N. Solovjeva ◽  
V.B. Gurvich ◽  
...  
Keyword(s):  
Nickel Oxide ◽  
Nervous Activity ◽  
Equal Mass ◽  
The Body ◽  
Subchronic Toxicity ◽  
Physiological Mechanisms ◽  
Nickel Oxide Nanoparticles ◽  
The Relationship ◽  
The Brain ◽  
Nanoparticles Toxicity

We conducted a comparative assessment of the nickel oxide nanoparticles toxicity (NiO) of two sizes (11 and 25 nm) according to a number of indicators of the body state after repeated intraperitoneal injections of these particles suspensions. At equal mass doses, NiO nanoparticles have been found to cause various manifestations of systemic subchronic toxicity with a particularly pronounced effect on liver, kidney function, the body’s antioxidant system, lipid metabolism, white and red blood, redox metabolism, spleen damage, and some disorders of nervous activity allegedly related to the possibility of nickel penetration into the brain from the blood. The relationship between the diameter and toxicity of particles is ambiguous, which may be due to differences in toxicokinetics, which is controlled by both physiological mechanisms and direct penetration of nanoparticles through biological barriers and, finally, unequal solubility.

Simultaneous Determination of Imatinib and N-Desmethyl Imatinib in Rat Plasma and Tissues Using LC-MS/MS

2019 ◽  
Vol 15 (2) ◽  
pp. 121-129
Author(s):  
Zhi Rao ◽  
Bo-xia Li ◽  
Yong-Wen Jin ◽  
Wen-Kou ◽  
Yan-rong Ma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Oral Administration ◽  
Parent Drug ◽  
Gradient Elution ◽  
Biological Tissues ◽  
Rat Plasma ◽  
Running Water ◽  
Liver And Kidney ◽  
The Brain

Background: Imatinib (IM) is a chemotherapy medication metabolized by CYP3A4 to Ndesmethyl imatinib (NDI), which shows similar pharmacologic activity to the parent drug. Although methods for determination of IM and/or NDI have been developed extensively, only few observations have been addressed to simultaneously determine IM and NDI in biological tissues such as liver, kidney, heart, brain and bone marrow. Methods: A validated LC-MS/MS method was developed for the quantitative determination of imatinib (IM) and N-desmethyl imatinib (NDI) from rat plasma, bone marrow, brain, heart, liver and kidney. The plasma samples were prepared by protein precipitation, and then the separation of the analytes was achieved using an Agilent Zorbax Eclipse Plus C18 column (4.6 × 100 mm, 3.5 µm) with gradient elution running water (A) and methanol (B). Mass spectrometric detection was achieved by a triplequadrupole mass spectrometer equipped with an electrospray source interface in positive ionization mode. Results: This method was used to investigate the pharmacokinetics and the tissue distributions in rats following oral administration of 25 mg/kg of IM. The pharmacokinetic profiles suggested that IM and NDI are disappeared faster in rats than human, and the tissue distribution results showed that IM and NDI had good tissue penetration and distribution, except for the brain. This is the first report about the large penetrations of IM and NDI in rat bone marrow. Conclusion: The method demonstrated good sensitivity, accuracy, precision and recovery in assays of IM and NDI in rats. The described assay was successfully applied for the evaluation of pharmacokinetics and distribution in the brain, heart, liver, kidney and bone marrow of IM and NDI after a single oral administration of IM to rats.

The musculature and nervous system of the plerocercoid larva of Dibothriorhynchus grossum (Rud.)

Parasitology ◽  
1941 ◽  
Vol 33 (4) ◽  
pp. 373-389 ◽  
Author(s):  
Gwendolen Rees
Keyword(s):  
Nervous System ◽  
Muscle Mass ◽  
Nerve Cells ◽  
The Body ◽  
Lateral Nerve ◽  
Posterior Median ◽  
The Brain ◽  
Ventral Muscle ◽  
Nerve Cords ◽  
Extrinsic Muscles

1. The structure of the proboscides of the larva of Dibothriorhynchus grossum (Rud.) is described. Each proboscis is provided with four sets of extrinsic muscles, and there is an anterior dorso-ventral muscle mass connected to all four proboscides.2. The musculature of the body and scolex is described.3. The nervous system consists of a brain, two lateral nerve cords, two outer and inner anterior nerves on each side, twenty-five pairs of bothridial nerves to each bothridium, four longitudinal bothridial nerves connecting these latter before their entry into the bothridia, four proboscis nerves arising from the brain, and a series of lateral nerves supplying the lateral regions of the body.4. The so-called ganglia contain no nerve cells, these are present only in the posterior median commissure which is therefore the nerve centre.

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