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Influence of Genetic Polymorphisms on the Pharmacokinetics of Trazodone Hydrochloride: A Scoping Review and Future Perspective.
Ther Drug Monit
August 2023
Department of Clinical Pathology, School of Medical Sciences, University of Campinas, Campinas.
Background: Trazodone hydrochloride is an antidepressant used in clinical practice. As a substrate of cytochrome P450 enzymes that is vulnerable to P-glycoprotein transport, several factors can alter its plasma concentration, and hence, dose adjustment may be required. The aim of this scoping review was to identify genetic polymorphisms that influence the pharmacokinetics of trazodone hydrochloride.
View Article and Find Full Text PDFAnxiolytic activity of a novel potent serotonin 5-HT2C receptor antagonist FR260010: a comparison with diazepam and buspirone.
Eur J Pharmacol
December 2006
Pharmacology Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305 -8585, Japan.
Hyperfunction of brain 5-hydroxytryptamine(2C) (5-HT(2C)) receptor is suggested to be involved in anxiety as evidenced by the fact that a putative 5-HT(2C) receptor agonist 1-(m-chlorophenyl)-piperazine (m-CPP) causes anxiety in humans. We have recently identified FR260010 (N-[3-(4-methyl-1H-imidazol-1-yl)phenyl]-5,6-dihydrobenzo[h]quinazolin-4-amine dimethanesulfonate) as novel 5-HT(2C) receptor antagonist from diaryl amine derivatives, and here characterized in vitro and in vivo profiles of the compound. FR260010 showed high affinity for human 5-HT(2C) receptor (K(i): 1.
View Article and Find Full Text PDFSerotonergic systems associated with arousal and vigilance behaviors following administration of anxiogenic drugs.
Neuroscience
October 2005
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
Serotonergic systems play important roles in modulating behavioral arousal, including behavioral arousal and vigilance associated with anxiety states. To further our understanding of the neural systems associated with increases in anxiety states, we investigated the effects of multiple anxiogenic drugs on topographically organized subpopulations of serotonergic neurons using double immunohistochemical staining for c-Fos and tryptophan hydroxylase combined with topographical analysis of the rat dorsal raphe nucleus (DR). Anxiogenic drugs with diverse pharmacological properties including the adenosine receptor antagonist caffeine, the serotonin 5-HT2A/2C receptor agonist m-chlorophenyl piperazine (mCPP), the alpha2-adrenoreceptor antagonist yohimbine, and the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) induced increases in behavioral arousal and vigilance behaviors consistent with an increase in anxiety state.
View Article and Find Full Text PDFRelationship between anorexia and loss of serotonin uptake sites in brain of mice and rats receiving d-norfenfluramine or d-fenfluramine.
Pharmacol Biochem Behav
March 2004
Department of Psychology, University of Florida, POB 112250, Gainesville, FL 32611-2250, USA.
Previously, we have shown that repeated administration of d-fenfluramine (D-F) to rats is associated with development of tolerance to the initial anorexia, but that in mice no such tolerance seems to occur. In the first study, we show that chronic administration of neither d-norfenfluramine (D-NF; the principal metabolite of D-F) nor the serotonin (5-HT) 2C receptor agonist m-chlorophenyl-piperazine (mCPP) is associated with the development of anorectic tolerance tested using a dessert protocol. However, compared with mice receiving these drugs for the first time, both of these chronic treatments were associated with a significant attenuation of Fos immunoreactivity (Fos-ir) in several brain regions, including bed nucleus of the stria terminalis, paraventricular hypothalamus, and central nucleus of amygdala.
View Article and Find Full Text PDFNeuroanatomical targets of anxiogenic drugs in the hindbrain as revealed by Fos immunocytochemistry.
Neuroscience
September 2000
University Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford, UK.
It is speculated that specific hindbrain transmitter pathways centred on the periaqueductal gray and locus coeruleus are an important integrative neural substrate for the expression of anxiety and the somatic symptoms and cardiovascular changes that accompany severe anxiety states, such as in panic disorder. Here we investigated the effects of various drugs, known to induce panic in humans and to be anxiogenic in animals, on Fos expression in the periaqueductal gray, locus coeruleus and other parts of the rat hindbrain. The drugs tested were the benozodiazepine inverse agonist FG-7142, the alpha(2)-adrenoceptor antagonist yohimbine, the non-selective 5-hydroxytryptamine(2C) receptor agonist m-chlorophenyl piperazine, the adenosine antagonist caffeine and the cholecystokinin analogue BOC-CCK(4).
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