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ADME studies and preliminary safety pharmacology of LDT5, a lead compound for the treatment of benign prostatic hyperplasia BJMBR
Noël,F.; Nascimento-Viana,J.B.; Romeiro,L.A.S.; Silva,R.O.; Lemes,L.F.N.; Oliveira,A.S.; Giorno,T.B.S.; Fernandes,P.D.; Silva,C.L.M..
This study aimed to estimate the absorption, distribution, metabolism and excretion (ADME) properties and safety of LDT5, a lead compound for oral treatment of benign prostatic hyperplasia that has previously been characterized as a multi-target antagonist of α1A-, α1D-adrenoceptors and 5-HT1A receptors. The preclinical characterization of this compound comprised the evaluation of its in vitro properties, including plasma, microsomal and hepatocytes stability, cytochrome P450 metabolism and inhibition, plasma protein binding, and permeability using MDCK-MDR1 cells. De-risking and preliminary safety pharmacology assays were performed through screening of 44 off-target receptors and in vivo tests in mice (rota-rod and single dose toxicity). LDT5 is stable in...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Benign prostatic hyperplasia; ADME; Safety; Permeability; CYP; Preclinical development.
Ano: 2016 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2016001200603
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Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum BJMBR
Noël,F.; Geurts,M.; Maloteaux,J.-M..
Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic...
Tipo: Info:eu-repo/semantics/other Palavras-chave: Ryanodine; Striatum; 6-hydroxydopamine; Dopamine neurons; Neuroleptic malignant syndrome.
Ano: 2000 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2000000200013
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Lack of evidence for regulation of cardiac P-type ATPases and MAP kinases in transgenic mice with cardiac-specific overexpression of constitutively active α1B-adrenoceptors BJMBR
Barreto,F.; Rezende,D.C.; Scaramello,C.B.V.; Silva,C.L.M.; Cunha,V.M.N.; Caricati-Neto,A.; Jurkiewicz,A.; Noël,F.; Quintas,L.E.M..
The regulatory function of α1B-adrenoceptors in mammalian heart homeostasis is controversial. The objective of the present study was to characterize the expression/activity of key proteins implicated in cardiac calcium handling (Na+/K+-ATPase and Ca2+-ATPases) and growth (ERK1/2, JNK1/2 and p38) in mice with cardiac-selective overexpression of constitutively active mutant α1B-adrenoceptor (CAMα1B-AR), which present a mild cardiac hypertrophy phenotype. Immunoblot assays showed that myocardial plasma membrane Ca2+-ATPase (PMCA) expression was increased by 30% in CAMα1B-AR mice (N = 6, P < 0.05), although there was no change in sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2) expression. Moreover, total Ca2+-ATPase activity was not modified, but a...
Tipo: Info:eu-repo/semantics/article Palavras-chave: Α1B-adrenoceptors; Ca2+-ATPases; Cardiac hypertrophy; Na+/K+-ATPase; Mitogen-activated protein kinases.
Ano: 2010 URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000500012
Registros recuperados: 3
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