Effect of chlorpromazine, imipramine and lithium on MAO-A and MAO-B activity in rat brain mitochondria.

Drugs with efficacy in psychiatric disorders affect the function of central neurotransmitter amines, which are inactivated primarily by monoamine oxidase (MAO). Effect of these drugs on the two types of MAO (MAO-A and MAO-B) has been studied in rat brain. The result showed that chlorpromazine (CPZ) and imipramine (IMI) at concentrations of 1x10(-2), 5x10(-3) and 2.5x10(-3) M inhibited rat brain mitochondrial MAO-A activity in vitro by 82, 50, 39 and 86, 74, 38 %, respectively. CPZ at concentrations of 5x10(-3), 2.5x10(-3), 1x10(-3) M inhibited rat brain mitochondrial MAO-B activity in vitro by 83, 55, 39 %, respectively, while IMI at concentrations of 5x10(-4), 2.5x10(-4), 1x10(-4) M inhibited the in vitro enzyme activity by 43, 35, 21 %, respectively. Lithium at concentration of 5x10(-3) M could not either inhibit MAO-A or MAO-B in the mitochondrial fraction of rat brain.

An outbreak of Eltor cholera in Aizwal town of Mizoram, India.

During the months of May, June and through early part of July 1994, an unusual occurrence of severe dehydrating watery diarrhoea cases and deaths were reported from Aizwal town, the capital of Mizoram, a North-Eastern state of India. Vibrio cholerae 01 biotype Eltor, the causative agent responsible for this outbreak, was isolated from 50.0% of hospitalised cases. The disease affected older children and adults more (52.9%) than younger children below five years of age. Vibrio cholerae 01 strains isolated were uniformly resistant to furazolidone and co-trimoxazole, which are commonly advocated in the treatment of cholera specially in children of developing countries. Emergence of such resistant strain is alarming and is of great public health importance.

Moclobemida - Interaçöes medicamentosas / Moclobemide: Pharmacokinetic interactions

Este artigo tem o escopo de mostrar a moclobemida, um inibidor reversível da MAOA apresenta um baixo perfil de interaçöes medicamentosas, principalmente no que tange à farmacodinâmica ocupando lugar de destaque na prática clínica para o tratamento de depressäo e alguns transtornos ansiosos

Inhibidores enzimáticos en el tratamiento de la enfermedad de Parkinson / Enzymatic inhibitors in the treatment of Parkinson's disease

La introducción de la L-DOPA en el tratamiento de los pacientes con enfermedad de Parkinson produjo un dramático impacto en la historia natural de esta enfermedad. Sin embargo su empleo crónico se asocia con la aparición de fluctuaciones motoras, describiéndose además una capacidad neurotóxica de la Dopamina. Ambos factores promueven la investigación constante de nuevos fármacos que permitan estabilizar los niveles plasmáticos de la L-DOPA y reducir las dosis útiles necesarias. Los inhibidores de la monoaminooxidasa (MAO) y de la catecol-oxi-metiltransferasa (COMT) permiten disminuir la degradación de la Dopamina contribuyendo a aumentar su biodisponibilidad y reducir las dosis de L-DOPA. Los inhibidores de la COMT aparecen como nuevos adjuvantes seguros y eficaces de la terapia antiparkinsoniana, pudiendo actuar a nivel central y periférico. Estas nuevas herramientas farmacológicas están destinadas a disminuir los efectos deletéreos que a largo plazo acarrea la L-DOPA terapia

Neuropharmacological studies on Fusarium toxins-III: Neurochemical investigations on total toxin extracts from F. moniliforme and F. oxysporum.

Neurochemical effects of different fusarial toxins elaborated from F. moniliforme (FM) and F. oxysporum (FO) were investigated. FM showed significant nonspecific and irreversible monoamine oxidase (MAO) inhibition which was qualitatively comparable to that induced by nialamide, a nonselective MAO inhibitor. FO did not exhibit any significant MAO inhibitory effect. FM produced a dose related increase in monoamine concentrations (dopamine, noradrenaline and 5-hydroxytryptamine) in different rat brain areas namely, diencephalon-midbrain, caudate nucleus and pons-medulla. FO, on the contrary, produced marked increase in dopamine concentration in the caudate nucleus with concomitant reduction in noradrenaline levels in diencephalon-midbrain and pons-medulla with little effect on 5-HT concentration. The neurochemical effects of FM and FO are consonant with the earlier reports on the neuropharmacological profile of these toxins. Thus, FM was reported to have nialamide like activity, whereas FO actions were dopaminergic in nature.

Neuropharmacological studies on Fusarium toxins--I: Total toxin extract from Fusarium moniliforme.

The neuropharmacological profile of the total fungal extract of F. moniliforme (FM) has been investigated. FM produced dose related decrease in spontaneous motor activity (SMA) and exploratory activity, potentiated pentobarbitone hypnosis and the anticonvulsant actions of phenobarbitone and phenytoin against MES seizures, potentiated PTZ and tryptamine seizures, antagonised reserpine induced syndrome, attenuated tetrabenazine and morphine induced catalepsy and potentiated haloperidol catalepsy. FM showed per se antinociceptive activity and potentiated morphine analgesia. It increased rectal temperature, antagonised reserpine and apomorphine hypothermia and potentiated the hyperthermic response of haloperidol and 5-hydroxytryptophan (5-HTP) and hypothermic response of betaphenylethylamine (PEA) and L-dopa. FM had no per se effect on amphetamine lethality, but enhanced the lethality induced by morphine in aggregated animals. Stereotypy by amphetamine was potentiated while that of apomorphine was not affected. The behavioural response of 5-HTP and L-dopa was potentiated. FM had no effect on swim induced behavioural despair. The effect on aggressive behavior was complex, and while the cumulative aggressive score was reduced, the onset of fighting behaviour and contact period was increased. It also inhibited clonidine induced auto mutilation. Since earlier investigation had shown that FM, like nialamide, induced non-selective inhibition of monoamine oxidase (MAO), the results were compared with those induced by nialamide. A comparative profile of action reveals that the neuropharmacological action of FM are qualitatively similar to those induced by nialamide, and likely to be due to inhibition of MAO. The investigation has practical implications because F. moniliforme is a common contaminant of cereals and fruits.

El efecto de un inhibidor de la xantinoxidasa asociado a la inhibición reversible de la monoaminoxidasa en el daño renal por isquemia reperfusión / The effect of a xanthine oxidase inhibitor associated to the reversible inhibition of monoamine oxidase in renal failure by ischemic-reperfusion

Diversas sustancias han mostrado efectividad en la protección del daño renal por isquemia-reperfusión. La inhibición de la xantínoxidasa (XO) por alopurinol (ALO) ha sido una de las más estudiadas. Previamente, mostramos el efecto protector de la Moclobemida (MOC), un inhibidor reversible de la monoaminoxidasa (MAO). El propósito del presente trabajo fue evaluar la asociación MOC + ALO sobre la función renal en un modelo de isquemia-reperfusión. Cincuenta ratas Sprague Dowley fueron sometidas a 60 minutos de clampeo de la arteria renal derecha y nefrectomía izquierda.El grupo I recibió MOC (100 mg/Kg) en cuatro dosis perioperatorias; el grupo II recibió ALO (50 mg/Kg) en una dosis previa al clampeo arterial y el grupo III recibió los dos esquemas (MOC + ALO). Los tres grupos tratados presentaron un descenso significativo de la creatinina plasmática en relación al control durante todo el período de insuficiencia renal (p < 0.001 para todos los días). Los grupos I y III presentaron una creatinina plasmática inferior al grupo II el primer día (grupo I: 1.64; grupo III: 1,51 v/s grupo II: 3,12; p < 0.001). Los grupos tratados con MOC presentaron una curva de insuficiencia renal más plana y una recuperación funcional más rápida. El grupo III mostró un leve efecto adivitivo. Se concluye que MOC es muy efectiva y superior a ALO en proteger la función renal. El efecto aditivo de la asociación MOC + ALO no es significativo en este modelo

Estudo brasileiro duplo-cego da eficácia e segurança da moclobemida versus imipramina no tratamento de pacientes com depressäo geriátrica / A double-blind Brazilian study of efficacy and safety of moclobemide versus imipramine in the treatment of patients with geriatric depression

A eficácia da moclobemida em pacientes ambulatoriais com depressäo geriátrica foi avaliada, num estudo controlado duplo-cego em comparaçäo com a imipramina. Os resultados obtidos com a moclobemida no tratamento de episódios depressivos maiores em pacientes idosos foram equivalentes àqueles obtidos com a imipramina, segundo os parâmetros de avaliaçäo do grau de depressäo. Na populaçäo estudada o uso de moclobemida esteve menos associado ao surgimento de efeitos anticolinérgicos e tonturas do que a imipramina. Cefaléia e fadiga foram mais freqüentes entre os pacientes que receberam moclobemida embora estes sintomas tenham sido leves e transitórios e bem tolerados. O ECG fos pacientes em uso de moclobemida näo se modificou durante a investigaçäo para o tratamento de depressäo geriátrica, pela sua eficácia e boa tolerabilidade

In vivo effects of isatin on certain enzymes, lipids & serotonergic system of rat brain.

Isatin (10 microM) strongly inhibited the activity of rat brain monoamine oxidase-B (MAO-B) in vitro. At millimolar concentrations (1-10 mM) it inhibited brain acetylcholinesterase (AChE) and sodium, potassium-adenosine triphosphatase (Na+, K(+)-ATPase) activity also. However, isatin did not affect these enzymes after both acute and chronic treatments in vivo. Administration of isatin to rats at 300 mg/kg body weight for 2 and 6 h significantly raised brain serotonin levels. Chronic treatment for 20 days resulted in enhanced brain glycolipids and plasmalogen levels. There was no change in the levels of 5-hydroxy indole acetic acid (5 HIAA), phospholipids, cholesterol and gangliosides under these conditions.

Actualización de psicofarmacología de la depresión / An update on depression psychopharmacology

Se analizan los diferentes grupos de fármacos de acción antidepresiva según su estructura química: tricíclicos, tetracíclicos, inhibidores de la monoamino-oxidasa (MAO) y los no clasificables. Se establecen los mecanismos de acción sobre los neurotransmisores cerebrales, según una clasificación bioquímica. Se enfatiza la importancia que el médico clínico se base en la sintomatología depresiva del enfermo según una clasificación sintomática, para la elección del fármaco a usar. Se analizan los efectos colaterales y las contraindicaciones que tienen mayor importancia en el uso de los fármacos antidepresivos según el tiempo de enfermo y según la patología concomitante. Se reseñan los tratamientos de las diferentes formas de depresión, señalando algunas instrucciones especiales que deben considerarse en cada caso

Effects of central epinephrine synthesis inhibition on stress-induced prolactin secretion in male rats

1. The present study was designed to examine the role of central epinephrine pathways in the control of stress-induced prolactin secretion in male adulto Wistar rats. 2. Intracerebroventricular adminsitration of two epinephrine synthesis inhibitors, SKF64139 (5 and 10 µg/rat) and LY 134046 (10 and 20 µg/rat), 6 h before the onset of immobilization stress blocked prolactin secretion in a dose-dependent manner. Prolactin values before stress were about 4.0 ng/ml and increased to almost 50 ng/ml in the control group. SKF 64139 injection in the higher dose (10 µg/rat) induced a complete blockade of the stress-induced prolactin release, whereas partial blockade was observed after the higher dose (20 µg/rat) of LY 134046. 3.Salbutamol pretreatment (10 µg/rat) completely restored stress-induced prolactin secretion in animals receiving a central injection of both epinephrine synthesis inhibitors under the same conditions as described above. 4. It is suggested that epinephrine pathways in the brain play an important role in the control of prolactin release occuring during immobilization stress

La eficacia antidepresiva y la tolerancia del moclobemide, un inhibidor reversible de la monoaminoxidasa / Antidepressive eficacy and tolerance of moclobemide amonoaminoxidasa reversible inhibitor

Los inhibidores de la Monoaminoxidas (MAOs) han resurgido recientemente como medicamentos de gran utilidad para el tratamiento de la depresión. Los riesgos de crisis hipertensivas y las restricciones dietéticas, que habían limtado su uso en el pasado, han sido reconsiderados com base en datos reciente, encontrándose que con ciertas precauciones, los IMAQs son medicamentos de gran utilidad y sobre todos seguros. Apesar de que se utilizan principalmente para el tratamiento de las depresiones neuróticas no endógenas, cuando se administran a dosis suficientes son tan efectivos como los tricíclicos, para el manejo de la depresión mayor y la depresión con melancolía. Por otra parte, se ha determinado que existen ciertos tipos de depresión en que los IMAOs tienen una indicación específica en que los IMAOs tienen una indicación específica. Entre ellos se pueden mencionar los estados depresivos que se acompañan de crisis de angustia, y la llamada depresión con perfil de disforia histeroides, que se manifiesta con sensibilidad, dificultades interpersonales, anergia y rasgos histéricos de personalidad. También las depresiones denominadas antípicas, caracterizadas por hiperfagia, hipersomnia y predominio vespertino de los síntomas, parecen responder mejor al tratamiento antidepressivo con IMAO. La Monoamonoxidasa (IMAO) es una enzima localizada en todos los sistemas del organismo. El cerebro, la MAO cataliza la degradación de transmisores monoanérgicos tales como la Noradrenalina (NA), la Dopamina (DA) y la Serotonina (5TH), permitiendo un mecanismo fisiológico de control para el mantenimiento del equilibrio entre la producción y la demanda de neurotransmisores en la sinapsis neuronal. Los IMAOs convencionales forman un complejo estable con la IMAO, inactivándola en forma irreversible; en consecuencia, los neurotransmisores degredados a una velocidad disminuida, incrementándose así sus concentraciones sinápticas...

Comparison of the effects of nalbuphine, fentanyl and pethidine in rabbits pretreated wilth a monoamine oxidase inhibitor tranylcypromine [parnate]

The existence of a severe toxic interaction from the clinical use of pethidine and monoamine oxidase [MAO] inhibitors is well known. The present study evaluates the possibility of such an interaction for the opioid partial agonist Nalbuphine and the pure agonist fentanyl. Conscious rabbits [n = 6] in each group pretreated 24 hours previously with physiological saline or the MAO inhibitor tranylcypromine [Parnate] 1.5 mg/kg S.C. were subsequently given physiological saline, pethidine 5 mg/kg, fentanyl 0.02 mg/kg and effect and parnate produced only a small increase in the rabbits temperature, the combination of parnate and pethidine produced a marked hyperpyrexia [+ 4.4 +/- 0.19°C, P < 0.001], hypertension 33.9 +/- 3.1 mmHg; P < 0.01] and agitation. Two rabbits died at 40 and 50 minutes after the pethidine- parnate combination. Nalbuphine and fentanyl were without significant effects on the parameters when given after the MAO-inhibitor parnate