Benzodiazepine receptor binding: Influence of physiologic and pharmacologic factors

Miller, Lawrence G.; Greenblatt, David J.; Shader, Richard I.

doi:10.1002/bdd.2510080202

Cited by 24 publications

(2 citation statements)

References 92 publications

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“…No significant correlation was found between age and specific [3H]-FNT binding in controls, whereas significant negative correlations were found in the schizophrenic group in three brain areas: eye movement area (r=-0.69, P < 0.05); orbitofrontal area (r = -0.85, P < 0.001); secondary and tertiary visual cortex (r=-0.66, P < 0.05). The effects of age on BZ receptor characteristics in animal studies are conflicting, but most studies show little effect of aging on binding (Tsang et al 1982;Miller et al 1987;Niles et al 1988). The effect of aging on BZ receptors in human brain has not yet been sufficiently studied.…”

Section: Discussionmentioning

confidence: 92%

Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics

Kiuchi

Kobayashi

Takeuchi

et al. 1989

Eur Arch Psychiatr Neurol Sci

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[3H]-Flunitrazepam (FNT) binding was measured in the post-mortem brains of 13 chronic schizophrenics and 10 controls whose mean ages and death-to-freezing intervals were the same in each group. The specific binding of [3H]-FNT to the medial frontal cortex, orbitofrontal cortex, orbital cortex, medial and inferior temporal gyri, superior temporal gyrus, cornu Ammonis 1-3 and putamen was significantly higher in schizophrenics than in controls. Specific binding to the eye movement area (frontal eye field), motor cortex, lateral occipitotemporal gyrus, dentate gyrus of the hippocampus and secondary and tertiary visual cortex did not differ in the two groups. Type 1 benzodiazepine (BZ) binding sites in the superior temporal gyrus of schizophrenics, determined from the displacement of [3H]-FNT binding using a triazolopyridazine, CL 218,872 (200 nM), were significantly higher than in the control group. The increase in type 2 BZ binding sites was not significant. Antipsychotic or benzodiazepine medication did not appear to affect the results. There were significant correlations between specific [3H]-FNT binding and concentration of GABA (positive) and of glutamic acid (negative), specific [3H]-kainic acid binding (positive), activity of tyrosine hydroxylase (positive), and substance P-like immunoreactivity (positive) in many areas of the brain. The Bmax of [3H]-spiperone binding in the putamen was also correlated positively with specific [3H]-FNT binding. These data suggest that dysfunction of BZ receptors may be involved in the pathogenesis and some symptoms of chronic schizophrenia.

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Section: Discussionmentioning

confidence: 92%

Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics

Kiuchi

Kobayashi

Takeuchi

et al. 1989

Eur Arch Psychiatr Neurol Sci

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“…Flurazepam hydrochloride is a benzodiazepin derivative that is extensively used as a hypnotic agent throughout the world [1][2][3], Previous studies have demonstrated that the rate and extent of benzodiazepine up take from systemic blood into the central nervous system are important determinants of the time-course and intensity of clinical action [4][5][6][7][8][9][10]. The present study evaluated the pharmacokinetics of intravenous flurazepam in dogs and the rate and extent of flu razepam entry into cerebrospinal fluid (CSF).…”

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confidence: 99%

Pharmacokinetics and CSF Entry of Flurazepam in Dogs

et al. 1988

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Anesthetized dogs received a single 1.0-mg/kg intravenous dose of flurazepam hydrochloride, following which multiple blood and cerebrospinal fluid (CSF) samples were taken over the next 8 h. Concentrations of flurazepam and its metabolite, desalkylflurazepam, were determined by gas chromatography with electron-capture detection. Mean kinetic variables for flurazepam were: volume of distribution 7.9 1/kg, elimination half-life 2.3 h, clearance 37 ml/min/kg, serum free fraction 25% unbound. The metabolic product desalkylflurazepam appeared in serum in low concentrations, and was eliminated with a half-life of 4.9 h. Flurazepam rapidly entered CSF, then was eliminated in parallel with flurazepam in serum. However, the extent of entry into CSF was limited, with the mean ratio of area under the curve for CSF versus serum (0.24) nearly identical to the serum free fraction. Thus, intravenous flurazepam in dogs is characterized by extensive distribution, high clearance, and short half-life. Entry into CSF is rapid, and appears governed by passive diffusion. The extent of CSF entry is limited by protein binding in serum.

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Anticonvulsants

Scott¹

2003

Burger's Medicinal Chemistry and Drug Discovery

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This chapter reports on the current and prospective anticonvulsant agents: their chemical structures, chemical names, pharmacokinetic parameters, and proposed mechanism(s) of action. Theoretical principles on structure‐activity development are presented as well as a brief explanation of animal testing to predict anticonvulsant activity. A hypothetical anticonvulsant model is presented that, within limits, is useful in elucidating the spatial/structural requirements for anticonvulsant activity against generalized epilepsy.

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Benzodiazepine receptor binding: Influence of physiologic and pharmacologic factors

Cited by 24 publications

References 92 publications

Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics

Benzodiazepine receptors increase in post-mortem brain of chronic schizophrenics

Pharmacokinetics and CSF Entry of Flurazepam in Dogs

Anticonvulsants

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