RESUMEN
Acetyl-L-carnitine (ALCAR) and myo-inositol are reported to enhance motor activity in animal models; modulate membrane phospholipid metabolism (ALCAR and myo-inositol) and high-energy phosphate metabolism (ALCAR) back to normal; and be effective treatments of major depression in humans. Fish in general and zebra fish in particular present unique animal models for the in vivo study of high-energy phosphate and membrane phospholipid metabolism by noninvasive in vivo 31P NMR. This 31P NMR study of free-swimming zebra fish showed that both ALCAR and myo-inositol decreased levels of phosphodiesters and inorganic orthophosphate and increased levels of PCr in the fish. These findings demonstrate both ALCAR and myo-inositol modulate membrane phospholipid and high-energy phosphate metabolism in free-swimming zebra fish.
Asunto(s)
Acetilcarnitina/farmacología , Inositol/farmacología , Lípidos de la Membrana/metabolismo , Fosfatos/metabolismo , Fosfolípidos/metabolismo , Acetilcarnitina/uso terapéutico , Animales , Trastorno Depresivo/tratamiento farmacológico , Humanos , Espectroscopía de Resonancia Magnética , Actividad Motora/efectos de los fármacos , Organofosfatos/metabolismo , Fosfocreatina/metabolismo , Fósforo , Valores de ReferenciaRESUMEN
The idea of lithium's specificity for bipolar disorder was proposed in Cade's original work in 1949. Since then, many controlled studies have been performed, examining lithium for treatment of bipolar disorder and other psychiatric conditions. This review was undertaken to determine if the suggestion of lithium's specificity has support in the controlled studies conducted after Cade's initial proposal. Studies were selected in a Medline search, dating back to 1966 and also identified from the bibliography of some of these papers. The controlled trials with lithium for the treatment of mania and bipolar depression, unipolar depression, schizophrenia, and schizoaffective disorder were reviewed. The published studies with lithium in other neuropsychiatric conditions were also considered. Additionally, we reviewed literature on other therapeutic agents proposed for bipolar disorder, looking at their comparative effectiveness to lithium. The data analyzed give strong support for lithium's being most effective in bipolar disorder, with minimal or no therapeutic effects in other neuropsychiatric disorders. The neurochemical underpinnings of this specificity are being investigated, without conclusive findings to date. The study of this paradigm of specificity in neuropsychopharmacology research may lead to meaningful contributions to understanding the pathophysiology of bipolar disorder and may help to develop newer treatments for this condition.
Asunto(s)
Antimaníacos/farmacología , Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Litio/farmacología , Litio/uso terapéutico , Animales , Trastorno Bipolar/psicología , Química Encefálica , HumanosRESUMEN
Only two tests were specific for antipsychotic potential. All effective antipsychotics blocked pharmacologically induced locomotion and affected firing in the mesolimbic DA neurons. The remaining single- (Table 1) and repeated- (Table 2) dose tests identified the atypical antipsychotics. Clozapine, thioridazine, sulpiride, tiospirone, and molindone were atypical in both types of study. Pimozide, pipamperone, aceperon, methylperon, and clotiapine were atypical in single-dose studies, clopenthixol in repeated-dose studies. Since the biochemical abnormality causing psychoses is unknown, it may be that current methods of screening for new antipsychotics are inadequate and possibly inappropriate. If a neurotransmitter other than DA is the primary cause, then totally new tests may be needed. Present tests, especially those involving behavioral paradigms, may continue to select out compounds that cause EPS side-effects. New methods such as positron emission tomography scanning and other brain-imaging techniques hold the promise of studying specific types and subtypes of receptors in the living human brain. The recent discovery of chromosomal abnormalities in psychotic illness may provide new insights into the biochemical causes of such disorders and lead to completely new compounds that will be both safer and more effective. In the meantime we plan to review the literature on the clinical use of the compounds identified as atypical in this article and to develop research protocols to assess their efficacy in treatment-resistant psychoses and intractable conditions such as tardive dyskinesia.
Asunto(s)
Antipsicóticos/administración & dosificación , Evaluación Preclínica de Medicamentos/métodos , Animales , Antipsicóticos/farmacología , Estudios de Evaluación como Asunto , Metaanálisis como Asunto , RatasAsunto(s)
Antidepresivos/farmacología , Albuterol/farmacología , Albuterol/uso terapéutico , Animales , Antidepresivos/historia , Antidepresivos/uso terapéutico , Bromofeniramina/análogos & derivados , Bromofeniramina/farmacología , Bromofeniramina/uso terapéutico , Bupropión , Ensayos Clínicos como Asunto , Trastorno Depresivo/tratamiento farmacológico , Dibenzocicloheptenos/farmacología , Dibenzocicloheptenos/uso terapéutico , Evaluación Preclínica de Medicamentos , Fluoxetina/análogos & derivados , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Historia del Siglo XX , Humanos , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/uso terapéutico , Propiofenonas/farmacología , Propiofenonas/uso terapéutico , Psicofarmacología/historia , Receptores Adrenérgicos/efectos de los fármacos , Receptores de Serotonina/efectos de los fármacos , Trazodona/farmacología , Trazodona/uso terapéutico , ZimeldinaRESUMEN
The most widely known substances that have been investigated for treating cognitive deterioration in the aged are cerebral vasodilators, Gerovital H3, psychostimulants, "nootropics," neuropeptides, and neurotransmitters. The rationale for the choice of specific agents has shifted as our conceptions regarding the origins of cognitive decline have changed; we now know that most cognitive deterioration occurs independently of arteriosclerotic vascular changes. Substances currently being investigated because of their effects on brain electrophysiology, on neurohumoral processes, or on central neurotransmitters show promise.
Asunto(s)
Trastornos del Conocimiento/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Ensayos Clínicos como Asunto , Dihidroergotoxina/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica , Metilfenidato/uso terapéutico , Parasimpaticomiméticos/uso terapéutico , Péptidos/uso terapéutico , Piracetam/uso terapéutico , Procaína/uso terapéutico , Vasodilatadores/uso terapéuticoRESUMEN
The stereochemical and pharmacological properties of yohimbine and some of its isomers are briefly reviewed. Several pharmacological and physical properties of a selection of the isomers have been determined with a view to elucidating which might be important in the elaboration of the known behavioral effects produced by them. Activity is not dependent upon lipid solubility or on the ease of access to the central nervous system. The isomers are weak inhibitors of rat-brain acetylcholinesterase and weak antagonists at muscarinic cholinergic receptors. In the rat brain in vitro they do not possess significant monoamine oxidase-inhibiting properties nor do they inhibit the uptake of serotonin. They are relatively potent antagonists of 5HT on the rat isolated fundus preparation and their potency in this preparation may be related to their ability to produce behavioral and cardiovascular effects in man and dogs.
Asunto(s)
Yohimbina/análogos & derivados , Yohimbina/farmacología , Animales , Encéfalo/metabolismo , Carbacol/antagonistas & inhibidores , Inhibidores de la Colinesterasa , Hipotálamo/enzimología , Técnicas In Vitro , Masculino , Ratones , Modelos Moleculares , Inhibidores de la Monoaminooxidasa , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Ratas , Serotonina/metabolismo , Antagonistas de la Serotonina , Solubilidad , Sinaptosomas/metabolismo , Yohimbina/metabolismoRESUMEN
Eighty-two elderly subjects with significant cognitive impairment were randomly assigned to treatment with either hyperbaric oxygen, hyperbaric air, normobaric oxygen, or normobaric air. Treatment consisted of two 90-minute sessions a day for 15 consecutive days. Subjects were evaluated on measures of memory and intellectual capacity, as well as on psychiatric symptom rating scales. Results immediately after treatment and at one, two, three, and eight weeks following treatment did not show enhanced cognitive functioning or significantly greater symptom reduction in experimental subjects who received either normobaric or hyperbaric oxygen as compared to controls who received hyperbaric or normobaric air. There was also no evidence of differential treatment effects as a function of initial severity of illness, sex, response to a CO2 loading test, or presumed evidence of cerebrovascular disease.
Asunto(s)
Trastornos del Conocimiento/terapia , Oxigenoterapia Hiperbárica , Trastornos Mentales/psicología , Oxígeno/uso terapéutico , Anciano , Estudios de Evaluación como Asunto , Femenino , Humanos , Inteligencia , Arteriosclerosis Intracraneal/psicología , Masculino , Memoria , Persona de Mediana Edad , Trastornos Neurocognitivos/psicología , Escalas de Valoración PsiquiátricaAsunto(s)
Trastornos Mentales/tratamiento farmacológico , Anciano , Estimulantes del Sistema Nervioso Central/uso terapéutico , Circulación Cerebrovascular/efectos de los fármacos , Dihidroergotoxina/uso terapéutico , Humanos , Oxigenoterapia Hiperbárica , Neurotransmisores/fisiología , Procaína/uso terapéutico , Vasodilatadores/uso terapéuticoRESUMEN
The effect of p-chlorophenylalanine-treatment in rats receiving chronic treatment with tranylcypromine on brain serotonin and 5-hydroxyindoleacetic acid levels was examined. This treatment schedule was similar to that followed in depressed patients undergoing treatment with the monoamine oxidase inhibitor. PCPA completely obviated the elevation in serotonin and further reduced 5-HIAA levels of animals treated chronically with tranylcypromine. These effects correlated with PCPA-induced reversal in the clinical improvement achieved by tranylcypromine. In in vitro studies, tranylcypromine was found to inhibit 5-HT uptake into synaptosomes with a minimal action on the spontaneous release of the amine.
Asunto(s)
Encéfalo/metabolismo , Fenclonina/farmacología , Serotonina/metabolismo , Tranilcipromina/farmacología , Animales , Encéfalo/efectos de los fármacos , Ácido Hidroxiindolacético/metabolismo , Hipotálamo/metabolismo , Masculino , Ratas , Sinaptosomas/metabolismoRESUMEN
47 affectively ill psychiatric patients and their first-, second- and third-degree relatives were investigated by means of an interview and pedigree analysis to determine the incidence of psychiatric illness in their families. The percentage of psychiatric illness appeared greatest in families of bipolar and schizo-affective probands and least in families of unipolar depressives. In addition, we observed that often within a particular family constellation, more than one type of psychiatric illness (i.e., bipolar manic-depression, schizophrenia, alcoholism, etc.) was present. Morbidity risks varied from one affected family to another, indicating that the genetic risk components for some families are greater than for others. These findings are suggestive of multifactorial genetic disease but other genetic models are considered.
Asunto(s)
Síntomas Afectivos/genética , Trastorno Bipolar/genética , Esquizofrenia/genética , Alcoholismo/genética , Humanos , LinajeRESUMEN
Graded doses of marihuana were administered to five adults in a longitudinal repeated-measurements design. Speed of response was the basic parameter measured accross tests of increasing cognitive involvement. Marihuana produced significant dose-response effects of impaired performance in all test scores. However, single automatic motor abilities demonstrated greater sensitivity than tests of greater complexity. Evidence is presented for tolerance development.
Asunto(s)
Cannabis/farmacología , Cognición/efectos de los fármacos , Destreza Motora/efectos de los fármacos , Adulto , Relación Dosis-Respuesta a Droga , Dronabinol/farmacología , Tolerancia a Medicamentos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Fitoterapia , Placebos , Tiempo de Reacción/efectos de los fármacos , Sugestión , Percepción del Tiempo/efectos de los fármacos , Pruebas de Asociación de PalabrasRESUMEN
Male rats were implanted subcutaneously with a pellet containg 75 milligrams of morphine base or placebo, and naloxone hydrochloride (4 milligrams per kilogram of body weight) was administered 72 hours later. Treatment with delta-9-tetrahydrocannabinol (2, 5, or 10 milligrams per kilogram) 1 hour before maloxone administration significantly reduced the intensity of abstinence; the two higher doses blocked the appearance of wet shakes and escapes, diarrhea, and increased defecation. delta-9-Tetrahydrocannabinol did not induce abstinence itself, and prior treatment with cannabidiol was ineffective in reducing naloxoneprecipitated abstinence in animals with morphine pellets. These data suggest that delta-9-tetrahydrocannabinol may be of value in facilitating narcotic detoxification.
Asunto(s)
Cannabis/uso terapéutico , Dronabinol/uso terapéutico , Dependencia de Morfina , Fitoterapia , Síndrome de Abstinencia a Sustancias/prevención & control , Animales , Relación Dosis-Respuesta a Droga , Dronabinol/farmacología , Humanos , Masculino , Naloxona/antagonistas & inhibidores , Placebos , RatasRESUMEN
The effect of amphetamine and l-dopa was compared in 22-hr food- and water-deprived rats. Amphetamine produced marked anorexia, and l-dopa significantly reduced food intake at 200 mg/kg. Following pretreatment with RO 4-4602, a decarboxylase inhibitor, 100 mg/kg of l-dopa, a dose that did not significantly affect eating, produced marked anorexia. The anorectic effect of both amphetamine and l-dopa was antagonized by propranolol, a beta adrenergic antagonist. Phentolamine, an alpha-adrenergic antagonist, potentiated the anorectic effect of amphetamine and l-dopa. Haloperidol (0.1 mg/kg), a dopamine antagonist, failed to prevent the anorexia due to amphetamine but accentuated that due to l-dopa. Methysergide, a serotonin antagonist, also failed to prevent the anorexigenic effect of amphetamine. Finally, the administration of l-dopa with or without peripheral decarboxylase inhibition resulted in more than twice the increase in hypothalamic dopamine levels without significant changes in 5-HT or norepinephrine levels. The data show that the anorexigenic effect of amphetamine and l-dopa are similar and indicate a functional role for both norepinephrine and dopamine neurons in feeding behaviour in the rat.
Asunto(s)
Depresores del Apetito , Dextroanfetamina/farmacología , Dihidroxifenilalanina/farmacología , Conducta Alimentaria/efectos de los fármacos , Animales , Antimetabolitos/farmacología , Carboxiliasas/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Haloperidol/farmacología , Hidrazinas/farmacología , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Masculino , Metisergida/farmacología , Norepinefrina/metabolismo , Fentolamina/farmacología , Propranolol/farmacología , Ratas , Serotonina/metabolismo , Factores de TiempoRESUMEN
Racemic methadone hydrochloride was administered to male rats in daily subcutaneous injections of 10-30 mg/kg. Dependence, when assessed by naloxone challenge after 26 days, was quantitatively and qualitatively similar to that previously reported by us for rats implanted with a 75 mg morphine pellet for 72 hours. Abstinence scores in animals pretreated acutely with 10 mg/kg delta 9-THC one hour before naloxone were significantly less than those of a vehicle control group, and wet shakes and gastrointestinal signs of abstinence were blocked. These results extend previous observations of morphine abstinence attenuating properties of delta 9-THC to effects on animals dependent on methadone.
Asunto(s)
Cannabis/uso terapéutico , Dronabinol/uso terapéutico , Metadona , Fitoterapia , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Animales , Conducta Animal/efectos de los fármacos , Tolerancia a Medicamentos , Humanos , Masculino , Dependencia de Morfina/tratamiento farmacológico , Naloxona/farmacología , Ratas , Síndrome de Abstinencia a Sustancias/inducido químicamenteRESUMEN
The effect of treatment with the factor that inhibits the release of melanocyte stimulating hormone (MSH) identified as 1-prolyl-1-leucylglycinamide (MIF) on brain catecholamine synthesis was examined in normal and hypophysectomized rats. The tripeptide induced a dose-related increase in striatal dopamine synthesis in slices obtained from treated normal animals but not in hypophysectomized animals. Hypothalamic norepinephrine synthesis was unaltered by MIF treatment in normal as well as in hypophysectomized rats. In addition, dopamine and norepinephrine syntheses were depressed in untreated hypophysectomized animals, as compared to normal controls. These results constitute the first direct demonstration of a central neurochemical effect of a hypothalamic factor.