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1.
Ann N Y Acad Sci ; 965: 487-96, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12105124

RESUMO

Cell death and reactive oxygen species production have been suggested to be involved in neurodegeneration induced by the drugs of abuse. In this study we analyze the toxicity of the following drugs of abuse: heroin, morphine, d-amphetamine, and cocaine in undifferentiated PC12 cells, used as dopaminergic neuronal models. Our data show that opioid drugs (heroin and morphine) are more toxic than stimulant drugs (d-amphetamine and cocaine). Toxic effects induced by heroin are associated with a decrease in intracellular dopamine, an increase in DOPAC levels, and the formation of ROS, whereas toxic effects induced by amphetamine are associated with a decrease in intracellular dopamine and in ATP/ADP levels. In contrast with cocaine, both amphetamine and heroin induced features of apoptosis. The data suggest that the death of cultured PC12 cells induced by the drugs of abuse is correlated with a decrease in intracellular dopamine levels, which can be associated with an increased dopamine turnover and oxidative cell injury.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cromatina/efeitos dos fármacos , Dopamina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Cocaína/farmacologia , Dextroanfetamina/farmacologia , Heroína/farmacologia , L-Lactato Desidrogenase/análise , Modelos Animais , Morfina/farmacologia , Entorpecentes/farmacologia , Células PC12 , Feocromocitoma , Ratos
2.
Ann N Y Acad Sci ; 914: 303-10, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11085330

RESUMO

The adrenergic system has long been known to be activated in a situation of stress and thus during opiate withdrawal. A method for detoxification that decreases the stimulation of the sympathetic nervous system will prevent changes of catecholamine levels. Some of such methods have been developed. One of them uses direct transition from heroin to oral naltrexone after deep sedation with midazolam in conjunction with naloxone, droperidol, ondansetron, and clonidine treatment for 24 hours. Can such method prevent adrenergic changes? Moreover, 5-HT has been related to mood disorders. This study aims to determine plasma catecholamines and 5-HT before heroin withdrawal, during the day of the withdrawal, and at the ends of the first day, the first week, and the first 6 months. Forty-three patients with more than 6 years of drug abuse volunteered to seek help to detoxify. After clinical evaluation, blood samples were taken. Plasma catecholamines were isolated by standard alumina procedures and measured by high-performance liquid chromatography with electrochemical detection. Only for NE was there a significant decrease in the day of heroin withdrawal with deep sedation, followed the next day by an increase. During the following days, NE plasma concentrations returned slowly to basal levels. Epinephrine and dopamine plasma levels did not significantly change. Platelet 5-HT levels progressively decreased from the day before detoxification until the last period of observation. We also found that there were no abrupt changes in cardiovascular functions. In conclusion, our results suggest that this type of ultrarapid opiate detoxification prevents the dramatic activation of the autonomic nervous system.


Assuntos
Catecolaminas/sangue , Dependência de Heroína/sangue , Heroína/farmacocinética , Síndrome de Abstinência a Substâncias/sangue , Adulto , Análise de Variância , Vias de Administração de Medicamentos , Quimioterapia Combinada , Feminino , Dependência de Heroína/metabolismo , Humanos , Inativação Metabólica , Masculino , Naloxona/administração & dosagem , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Síndrome de Abstinência a Substâncias/metabolismo , Sístole , Resultado do Tratamento
3.
Fundam Clin Pharmacol ; 13(6): 662-70, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10626754

RESUMO

Electrical stimulation-induced depolarization releases both dopamine (DA) and noradrenaline (NA) from sympathetic neurones of the human gastric and uterine arteries. The overflow of catecholamines elicited by electrical stimulation was measured by using high performance liquid chromatography with electrochemical detection. The addition of yohimbine (0.01-10 microM), an alpha2-adrenoceptor antagonist, to the perfusion fluid increased, in a concentration-dependent manner, the electrically-evoked DA and NA overflow from gastric and uterine arteries. In the presence of sulpiride (0.01-10 microM), a dopamine D2-type receptor antagonist, the overflow of both amines was found to be increased in the uterine artery, but not in the gastric artery. Apomorphine (0.1-10 microM), a dopamine receptor agonist, produced a dose-dependent inhibition in the amount of DA and NA released from gastric and uterine arteries. SCH 23390 (0.1-10 microM), a dopamine D1 receptor antagonist, had no effect on the release of both amines in both preparations. The inhibitory effect of apomorphine was blocked by sulpiride in the gastric and uterine arteries but not by SCH 23390. The results presented suggest the existence of dopamine D2-type receptors in the human gastric and uterine arteries. They seem to have, in each artery, a different physiological importance.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Dopamina/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Norepinefrina/metabolismo , Receptores de Dopamina D2/efeitos dos fármacos , Receptores Pré-Sinápticos/efeitos dos fármacos , Ioimbina/farmacologia , Apomorfina/farmacologia , Artérias , Relação Dose-Resposta a Droga , Interações Medicamentosas , Estimulação Elétrica , Feminino , Humanos , Músculo Liso Vascular/metabolismo , Estômago , Sulpirida/farmacologia , Útero
4.
Mol Neurobiol ; 11(1-3): 21-9, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8561963

RESUMO

This work evaluated in a population of heroin and heroin plus cocaine human addicts: 1. Norepinephrine (NE), epinephrine (Epi) and 3-methoxy-4-hydroxyphenylglycol (MHPG) (the principal metabolite of brain NE) plasma levels; 2. Monoamine oxidase (MAO) activity; and 3. 3H-imipramine specific binding to the amine carrier in platelets. NE plasma levels were significantly lower in the short-term heroin user groups (1-3 and 4-6 yr), a finding not observed in both long-term heroin user ( > 6 yr) and heroin plus cocaine user ( > 6 yr) groups. Epi levels changed in a similar manner, except that a significant increase was noted in heroin plus cocaine abusers. Conversely, dopamine and MHPG plasma levels increased with the duration of heroin use, and even more with cocaine abuse. Platelet MAO activity increased in all groups. Specific 3H-imipramine binding sites showed an increase after 3 yr of heroin abuse and in all heroin plus cocaine addicts. In conclusion, short-term use of heroin decreases NE or Epi release, but with prolonged use, a slow adaptation occurs. In contrast, cocaine inhibits the neuronal Epi uptake, even in a situation of long duration of abuse. Probably the amine levels additionally regulate the amine carrier, resulting in changes that show a different pattern from major depression. These drugs of abuse may also influence directly or indirectly related enzymatic systems.


Assuntos
Plaquetas/enzimologia , Cocaína , Epinefrina/sangue , Dependência de Heroína/sangue , Imipramina/sangue , Metoxi-Hidroxifenilglicol/sangue , Monoaminoxidase/sangue , Norepinefrina/sangue , Transtornos Relacionados ao Uso de Substâncias/sangue , Adulto , Proteínas de Transporte/metabolismo , Feminino , Dependência de Heroína/enzimologia , Humanos , Masculino , Receptores de Droga/metabolismo , Valores de Referência , Transtornos Relacionados ao Uso de Substâncias/enzimologia , Trítio
5.
J Lipid Mediat ; 3(2): 167-75, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1797152

RESUMO

New Zealand White rabbits fed a low-level cholesterol-enriched diet (0.1%) were used to study and characterize a possible model of experimental atherogenesis. For the determination of the degree of atherosclerosis, more consistent and reproducible morphometric methods were used. Simultaneously the influence of plasma cholesterol levels on vascular noradrenaline content was studied. The effect of a new lipid-regulating drug (0.1% L 44-0, the N-oxide of a nicotinic acid derivative) on analyzed parameters was studied as well. This study suggests that the low-level cholesterol-enriched diet is atherogenic, with macroscopically detectable lesions of atherosclerosis becoming apparent by week 12 of the study. The same diet increases the vascular noradrenaline content in the renal artery and in the femoral artery and vein; however, it does not influence that content in the carotid and mesenteric arteries. L 44-0 counteracts most of the observed effects.


Assuntos
Arteriosclerose/fisiopatologia , Vasos Sanguíneos/química , Colesterol na Dieta/metabolismo , Óxidos N-Cíclicos/farmacologia , Modelos Animais de Doenças , Lipídeos/análise , Ácidos Nicotínicos/farmacologia , Norepinefrina/metabolismo , Animais , Arteriosclerose/induzido quimicamente , Colesterol/análise , Estudos de Avaliação como Assunto , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/metabolismo , Lipoproteínas HDL/análise , Masculino , Coelhos , Triglicerídeos/análise
6.
Cephalalgia ; 10(5): 213-9, 1990 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-2272090

RESUMO

In spite of recent theories about the aetiopathogenesis of migraine, serotonin continues to play a central role, explaining the efficacy of almost all migraine prophylactic drugs. In migraineurs with and without aura we measured (by HPLC-EC) the serum serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels between as well as during headache attacks. Between attacks of migraine with aura and at the beginning of attacks of both types of migraine the serum 5-HT and 5-HIAA concentration was significantly increased. These results were corroborated by 3H-spiperone binding to platelet membranes: in migraineurs with aura in the attack-free interval, there was a significant decrease in its Bmax, which suggests down-regulation of 5-HT2 receptors. In conclusion, we have verified that migraine with aura differs biochemically from migraine without aura.


Assuntos
Plaquetas/química , Transtornos de Enxaqueca/sangue , Receptores de Serotonina/sangue , Serotonina/sangue , Adolescente , Adulto , Criança , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Cinética , Pessoa de Meia-Idade , Agregação Plaquetária , Ensaio Radioligante
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