RESUMO
From the pro-inflammatory active extract of Euphorbia peplus, a new diterpene polyester (1) based on the jatrophane skeleton was isolated together with the known compounds 2-5. The irritant activities of some jatrophane diterpenes (2, 3 and 6-9) were also investigated: only compound 2 was found to exert a weak pro-inflammatory activity on mouse ear.
Assuntos
Diterpenos/química , Irritantes/química , Extratos Vegetais/química , Animais , Diterpenos/isolamento & purificação , Diterpenos/toxicidade , Orelha , Irritantes/isolamento & purificação , Irritantes/toxicidade , Camundongos , Estrutura Molecular , Extratos Vegetais/toxicidadeRESUMO
A new lathyrane diterpene (1) has been isolated and characterized from a CH2Cl2 extract of the roots of Euphorbia lathyris. Detailed spectral analysis revealed that the structure of 1, including relative stereochemistry, is that of a diester of a hitherto unknown, polyfunctional diterpene parent alcohol.
RESUMO
Three new jatrophane diterpenes, esulatin A, B and C (1-3) were isolated and characterized from the whole, undried plant of Euphorbia esula. By means of spectral analysis, the structures were established as penta- and heptaesters of hitherto unknown, polyfunctional diterpene parent alcohols. Esulatin A (1) and C (3) are the diterpenoids with the highest degree of esterification identified to date from the family Euphorbiaceae.
Assuntos
Diterpenos/química , Ésteres/química , Euphorbiaceae/química , Diterpenos/isolamento & purificação , Ésteres/isolamento & purificação , Estrutura MolecularAssuntos
Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Isoxazóis/uso terapêutico , Piperidinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Recidiva , Risperidona , Esquizofrenia Paranoide/tratamento farmacológicoRESUMO
Acetolysis of (Z)-1,3-di-O-acetyl-2,4-O-benzylidene-6-C-(2,4-dichlorophenyl)-D-xylo-he x- 5-enitol (3) afforded (E)-1,2,3,4-tetra-O-acetyl-6-C-(2,4-dichlorophenyl)-D-xylo-hex-5-enit ol and 2-C-[(R)-acetoxy(2,4-dichlorophenyl)methyl]-3,4,6-tri-O-acetyl-2-deoxy- beta-L-galacto- and -beta-L-gulo-hexopyranosylbenzene. The mechanism of this new rearrangement was studied by exchanging the substituents at C-1 and C-3 in 3 and those of the aromatic ring attached to C-6.
Assuntos
Derivados de Benzeno/química , Compostos de Benzilideno/química , Hexoses/química , Inibidores de Hidroximetilglutaril-CoA Redutases , Derivados de Benzeno/síntese química , Compostos de Benzilideno/síntese químicaRESUMO
Central nervous system (CNS) toxicity of tricyclic antidepressants (TCAs) is serious, costly, frequent, and difficult to diagnose early in its course. We first reviewed all published, systematic population studies of such CNS toxicity. Of 976 TCA-treated patients, 58 (6%) developed TCA-induced CNS toxicity. The risk of this toxicity was positively correlated with TCA plasma levels. For levels greater than 450 ng/ml, the risk increased more than 10-fold (to 67%). We further analyzed 36 cases in terms of phenomenology, course, and potential risk factors of TCA-induced toxicity. A protean prodrome involving affective, psychotic, and cognitive symptoms preceded the delirium, which on average took 2 weeks to develop. The variability of this prodrome often leads to erroneous clinical decisions. Risk factors for delirium, in order of importance, included TCA concentration in plasma, age, and female gender.
Assuntos
Antidepressivos Tricíclicos/efeitos adversos , Doenças do Sistema Nervoso Central/induzido quimicamente , Adolescente , Adulto , Idoso , Antidepressivos Tricíclicos/administração & dosagem , Antidepressivos Tricíclicos/sangue , Doenças do Sistema Nervoso Central/epidemiologia , Criança , Feminino , Humanos , Incidência , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Monitorização Fisiológica , Fatores de RiscoRESUMO
D-Galactose was converted into the glycosylating agents 4-azido-2,3-di-O-benzyl-4-deoxy-6-O-propionyl-alpha-D-glucopyranosyl chloride (11) and the methyl beta-D-thiopyranoside 19. Condensation of 11 with 2,5-diazido-1,6-di-O-benzoyl-2,5-di-deoxy-L-iditol in the presence of mercury salts gave 24% of 2,5-diazido-3-O-(4-azido-2,3-di-O-benzyl-4-deoxy-6-O-propionyl-alp ha-D- glucopyranosyl)-1,6-di-O-benzoyl-2,5-dideoxy-L-iditol. Methyl trifluoromethanesulfonate-promoted glycosylation of 1,3-diazido-2-O-benzyl-1,3-dideoxy-5,6-O-isopropylidene-D-gulit ol with 19 in the presence of 2,6-di-tert-butyl-4-methylpyridine gave 1,3-diazido-4-O-(4-azido-2,3-di-O-benzyl-4-deoxy-6-O-propionyl-alp ha-D- glucopyranosyl)-2-O-benzyl-1,3-dideoxy-5,6-O-isopropylidene-D-gulitol (42), whereas, in the absence of base, migration of the O-isopropylidene group occurred, affording 1,3-diazido-6-O-(4-azido-2,3-di-O-benzyl-4-deoxy-6-O-propionyl-alp ha-D- glucopyranosyl)-2-O-benzyl-1,3-dideoxy-4,5-O-isopropylidene-D-gulitol in addition to 42.
Assuntos
Aminoglicosídeos , Antibacterianos/síntese química , Compostos de Mercúrio , Brometos , Fenômenos Químicos , Química , Galactose , Glicosilação , Espectroscopia de Ressonância Magnética , Mercúrio , Estrutura Molecular , ÓxidosRESUMO
The traditional dose-response method of medication adjustment depends on several assumptions that are not met in the case of tricyclic antidepressants (TCAs), which makes therapeutic drug monitoring (TDM) particularly useful with these drugs. TDM can facilitate treatment by providing objective guidelines for dose adjustment. It provides a means of assessing compliance, ensuring an effective concentration, and avoiding toxicity. The latter is an often-overlooked benefit of therapeutic monitoring of TCAs and yet is just as important as improving response. The cardiac and central nervous system toxicity of TCAs is concentration-dependent and potentially life-threatening. Such toxicity will predictably occur in up to 5% of patients on standard antidepressant doses of TCAs when TDM is not used to rationally adjust the dose. Without TDM, such toxicity is difficult to detect early. A cost/benefit analysis supports the cost effectiveness of TDM as a standard part of TCA chemotherapy when doses in the 100-300 ng/day range are used.
Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Monitorização Fisiológica/economia , Antidepressivos Tricíclicos/efeitos adversos , Sistema Cardiovascular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Análise Custo-Benefício , Relação Dose-Resposta a Droga , HumanosRESUMO
The effects of amitriptyline, lithium, and electroconvulsive shock on cerebral permeability and blood flow were tested. These three treatments share in common (i) the ability to influence the functional activity of central adrenergic neurons by way of effects on the release, reuptake, or metabolism of norepinephrine and (ii) therapeutic efficacy in mood disturbances. Under control conditions, cerebral permeability increases linealy with increasing arterial partial pressure of carbon dioxide and hence cerebral blood flow. All three treatments altered this relationship in a manner consistent with their adrenergic effects. Amitriptyline potentiated this increase in cerebral permeability whereas lithium and electroconvulsive shock blunted this phenomenon. These results support the hypothesis that one function of central adrenergic neurons is regulation of the blood-brain barrier and raise the possibility that a related effect may underlie the clinical usefulness of such treatment.