Involvement of P-glycoprotein in Blood-Brain Barrier Transport of Pentazocine in Rats Using Brain Uptake Index Method

Moriki, Yoshiaki; Suzuki, Toyofumi; Fukami, Toshiro; Hanano, Manabu; Tomono, Kazuo; Watanabe, Jun

doi:10.1248/bpb.27.932

Cited by 20 publications

(15 citation statements)

References 21 publications

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“…In our study, the cortical levels of glycine reached 1376 ± 30 pmol/mg wet tissue (C max ), which was 2-fold higher than that observed in the vehicle controls after 4 h (T max ). For a detailed analysis, we investigated the glycine uptake into the brain using the brain uptake index (BUI) method (14,15). The brain uptake of glycine varied with respect to the injected quantities of glycine, ranging from 0.67 to 2.5 mmol/kg.…”

Section: The Pharmacokinetics Of Glycinementioning

confidence: 99%

New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep

Bannai

Kawai

2012

J Pharmacol Sci

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Abstract. Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine's effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials.

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Section: The Pharmacokinetics Of Glycinementioning

confidence: 99%

New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep

Bannai

Kawai

2012

J Pharmacol Sci

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“…In vivo glycine transportation across the BBB was evaluated after glycine injection into the carotid artery, as reported previously (Oldendorf 1970;Moriki et al 2004). [2-3 H]-glycine (37 MBq/mL) was purchased from PerkinElmer (Waltham, MA, USA), and carboxyl-14 C-inulin (3.7 MBq/ mL) was purchased from American Radiolabeled Chemicals Inc. (St. Louis, MO, USA).…”

Section: Experiments 2: Amino Acid Analysismentioning

confidence: 99%

“…The uptake amount and brain uptake index (BUI) of glycine were calculated using the method reported by Oldendorf (Oldendorf 1970;Moriki et al 2004), as described below. Formula 1 describes the concentration of distributed glycine in blood, and formula 2 describes its concentration in tissue.…”

Section: Experiments 2: Amino Acid Analysismentioning

confidence: 99%

Pharmacokinetics and cerebral distribution of glycine administered to rats

et al. 2011

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High doses of glycine have been reported to improve negative schizophrenic symptoms, suggesting that ingested glycine activates glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. However, the pharmacokinetics of administered glycine in the brain has not been evaluated. In the present study, the time- and dose-dependent distributions of administered glycine were investigated from a pharmacokinetic viewpoint. Whole-body autoradiography of radiolabeled glycine was performed, and time-concentration curves for glycine and serine in plasma, cerebrospinal fluid (CSF), and brain tissues were obtained. Furthermore, pharmacokinetic parameters were calculated. For a more detailed analysis, the amount of glycine uptake in the brain was evaluated using the brain uptake index method. Radiolabeled glycine was distributed among periventricular organs in the brain. Oral administration of 2 g/kg of glycine significantly elevated the CSF glycine concentration above the ED50 value for NMDA receptors. The glycine levels in CSF were 100 times lower than those in plasma. Glycine levels were elevated in brain tissue, but with a slower time-course than in CSF. Serine, a major metabolite of glycine, was elevated in plasma, CSF, and brain tissue. Glycine uptake in brain tissue increased in a dose-dependent manner. Time-concentration curves revealed that glycine was most likely transported via the blood-CSF barrier and activated NMDA receptors adjacent to the ventricles. The pharmacokinetic analysis and the brain uptake index for glycine suggested that glycine was transported into brain tissue by passive diffusion. These results provide further insight into the potential therapeutic applications of glycine.

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“…Pgp is a most thoroughly studied transport protein with broad specificity to structurally diverse lipophilic and amphiphilic compounds [281]. It restricts CNS entry of many drugs, such as HIV-1 protease inhibitors (ritonavir, nalfinavir, and indinavir) [282], anti-inflammatory agents (prednesolone, dexamethasone and indomethacin) [281,283], neuroleptics (amitriptyline and haloperidol) [284], analgesics (morphine, beta-endorphin, and asimadoline) [285], anti-epileptic agents (carbamazepine, phenobarbital, phenytoin, and lamotrigine) [286], and anti-fungal agents (itraconazole and ketoconazole) [287]. Moreover, delivery of many anti-cancer agents (doxorubicin, vinblastine, paclitaxel, etc.)…”

Section: Polymeric Inhibitors Of Drug Efflux Systems In Bbbmentioning

confidence: 99%

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

Kabanov

Gendelman

2007

Progress in Polymer Science

234

138

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Neurodegenerative and infectious disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population's age. Alzheimer's disease alone currently affects 4.5 million Americans, and more than $100 billion is spent per year on medical and institutional care for affected people. Such numbers will double in the ensuing decades. Currently disease diagnosis for all disorders is made, in large measure, on clinical grounds as laboratory and neuroimaging tests confirm what is seen by more routine examination. Achieving early diagnosis would enable improved disease outcomes. Drugs, vaccines or regenerative proteins present "real" possibilities for positively affecting disease outcomes, but are limited in that their entry into the brain is commonly restricted across the blood-brain barrier. This review highlights how these obstacles can be overcome by polymer science and nanotechnology. Such approaches may improve diagnostic and therapeutic outcomes. New developments in polymer science coupled with cell-based delivery strategies support the notion that diseases that now have limited therapeutic options can show improved outcomes by advances in nanomedicine.

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Involvement of P-glycoprotein in Blood-Brain Barrier Transport of Pentazocine in Rats Using Brain Uptake Index Method

Cited by 20 publications

References 21 publications

New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep

New Therapeutic Strategy for Amino Acid Medicine: Glycine Improves the Quality of Sleep

Pharmacokinetics and cerebral distribution of glycine administered to rats

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

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