RESUMO
Low blood pressure is frequent in the akinetic form of Parkinson's disease. A low renin activity in plasma as well as a low rate of aldosterone secretion is demonstrated in these patients. Renin activity in the plasma is further decreased by treatment with L-dihy-droxyphenylalanine, thus partially accouinting for the hypotensive episodes seen with this form of therapy.
Assuntos
Aldosterona/sangue , Di-Hidroxifenilalanina/uso terapêutico , Hipotensão/etiologia , Doença de Parkinson/sangue , Renina/sangue , Catecolaminas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sódio/farmacologia , TrítioRESUMO
A renin-like enzyme is present in brain tissue and is independent of kidney and plasma renin. In the presence of homologous substrate it forms angiotensin. Administration of aldosterone significantly decreases this angiotensinforming enzyme activity, while administration of progesterone markedly enhances it.
Assuntos
Angiotensina II/biossíntese , Núcleo Caudado/enzimologia , Renina/análise , Aldosterona/farmacologia , Animais , Química Encefálica , Núcleo Caudado/análise , Núcleo Caudado/efeitos dos fármacos , Depressão Química , Cães , Progesterona/farmacologia , Sódio/metabolismo , Estimulação QuímicaRESUMO
Stimulation and inhibition tests are proposed for evaluating prolactin secretion. Thyrotropin-releasing hormone (TRH) stimulates the release of prolactin from the pituitary. Chlorpromazine acts presumably at the hypothalamic level to increase prolactin secretion. L-Dopa (D,L-alpha-hydrazino-alpha-methyl-beta-[3,4-di-hydroxyphenyl]) has the opposite effect; it inhibits prolactin secretion and may be effective in suppressing galactorrhea.
Assuntos
Clorpromazina/farmacologia , Di-Hidroxifenilalanina/farmacologia , Transtornos da Lactação/tratamento farmacológico , Hipófise/efeitos dos fármacos , Prolactina/metabolismo , Hormônio Liberador de Tireotropina/farmacologia , Administração Oral , Adolescente , Adulto , Pré-Escolar , Clorpromazina/administração & dosagem , Di-Hidroxifenilalanina/administração & dosagem , Di-Hidroxifenilalanina/uso terapêutico , Feminino , Humanos , Injeções Intramusculares , Injeções Intravenosas , Masculino , Hipófise/metabolismo , Gravidez , Prolactina/antagonistas & inibidores , Prolactina/sangue , Radioimunoensaio , Tireotropina/sangue , Hormônio Liberador de Tireotropina/administração & dosagemRESUMO
The effects of intraventricular administration of neurotensin (0.9, 3.75 and 15.0 micrograms) on hyperactivity and stereotypy induced by either amphetamine (1 mg/kg), nomifensine (20 mg/kg), apomorphine (0.5 mg/kg) or N-n-propylnorapomorphine (0.5 mg/kg) were examined. Results indicate that for each drug treatment, the effects of neurotensin were identical: hyperactivity was significantly reduced while stereotypy remained unaffected. Results also revealed that neurotensin significantly increased the hypothermia induced by apomorphine and N-n-propylnorapomorphine. Possible mechanisms which could underly neurotensin's selective inhibitory action on hyperactivity produced by both pre and post synaptic dopaminergic stimulation are discussed.
Assuntos
Dopamina/fisiologia , Hipercinese/induzido quimicamente , Neurotensina/farmacologia , Comportamento Estereotipado/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Anfetamina/administração & dosagem , Animais , Apomorfina/administração & dosagem , Apomorfina/análogos & derivados , Humanos , Masculino , Nomifensina/administração & dosagem , Ratos , Ratos EndogâmicosRESUMO
The clinical course and the side effects of high-level levodopa therapy over a six-year period were studied in 80 severely akinetic parkinsonian patients treated for the first time before June 1968. Levodopa improved the quality of life in greater than 53% of patients, but failed to modify the progression of the disease or change the prognosis. Seventeen "idiopathic Parkinson" patients died after a duration of illness of 9.5 years. Despite the drawbacks, levodopa is still the best available treatment for akinetic parkinsonism.
Assuntos
Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Atividades Cotidianas , Avaliação de Medicamentos , Feminino , Humanos , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Assistência de Longa Duração , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/induzido quimicamente , Doença de Parkinson/mortalidade , Pacientes Desistentes do Tratamento , PrognósticoRESUMO
A combination of levodopa and a peripheral dopa-decarboxylase inhibitor, benzerazide (Ro 4-4602), was studied over a 75-month period of observation in 132 patients with Parkinson's disease. The combined therapeutic approach was without biological toxicity, was well tolerated by 95 percent of patients, and was highly effective: 72 percent of patients improved by more than 50 percent on a functional activity scale and the group as a whole improved on an objective battery by a mean of 46 percent. Neurologic side effects of abnormal involuntary movements, falls, and oscillations in performance were not improved over levodopa used alone. The combined therapy is to be preferred over the use of levodopa alone in the symptomatic management of Parkinson's disease.
Assuntos
Benserazida/uso terapêutico , Hidrazinas/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Benserazida/administração & dosagem , Benserazida/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/induzido quimicamente , Pacientes Desistentes do Tratamento , Fatores de TempoRESUMO
Thirty-five parkinsonian patients (five untreated, six with levodopa only, seven with levodopa plus Ro 4-4602, nine with anticholinergic and/or antihistaminic medication, and eight with the anticholinergic/antihistaminic medication plus amantadine) and 35 age-matched control subjects were studied. Platelets isolated from each individual plasma were incubated with 14C-dopamine. Uptake was found to be decreased to a significant degree in all treated or untreated parkinsonian patients when compared with control subjects. Anticholinergic and/or antihistaminic medication, with or without amantadine, further decreased the dopamine uptake into platelets, while levodopa alone or with Ro 4-4602 returned uptake values to near normal. Dopamine efflux paralleled exactly the uptake values. The fact that parkinsonian platelets exhibit impaired dopamine uptake, while age-matched control platelets do not, constitutes the first direct evidence in favor of a generalized dopamine defect in Parkinson's disease.
Assuntos
Plaquetas/metabolismo , Dopamina/metabolismo , Doença de Parkinson/metabolismo , Adulto , Idoso , Amantadina/farmacologia , Inibidores das Descarboxilases de Aminoácidos Aromáticos , Benserazida/uso terapêutico , Radioisótopos de Carbono , Depressão Química , Sinergismo Farmacológico , Quimioterapia Combinada , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Levodopa/administração & dosagem , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Parassimpatolíticos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fatores de Tempo , Triexifenidil/farmacologiaRESUMO
Effects of taurine or gamma-aminobutyric acid (GABA) on akinesia and analgesia induced by D-Ala2-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375 X 10(-2) M-9.5 X 10(-2)-Met-enkephalinamide were investigated in rats. Administration of taurine (dose range: 2.375 X 10(-2) M-9.5 X 10(-2) M/10 microliters) into the left lateral ventricle 10 min prior to the injection of D-Ala2-Met enkephalinamide (50 microgram/10 microliter) produced a dose-dependent reduction in the duration of akinesia and to some extent of analgesia, as estimated at 30 min and 60 min following the enkephalinamide injection; at the first estimation-time (10 min), taurine did not alter the duration of akinesia or that of analgesia. The median effective dose (ED50) for akinesia determined at 60 min after D-Ala2-Met-enkephalinamide was 5 times greater and that for analgesia assessed at the same time was 1.7 times greater in taurine-treated rats than the respective doses in control animals. Administration of GABA under similar experimental conditions produced a dose-dependent reduction in the duration of analgesia from the initial estimation time (10 min) following the injection of D-Ala2-Met-enkephalinamide. The ED50 for analgesia determined at 30 min after D-Ala2-Met-enkephalinamide was 3 times greater in GABA-treated rats than in control animals. Unlike the effects of taurine, GABA did not alter the duration of akinesia. Neither the duration of akinesia nor that of analgesia was modified by taurine or GABA alone in rats tested 9 min after the injection of each amino acid. These findings suggest that taurine may promote a recovery from both akinesia and analgesia, while GABA decreases only the analgesia induced by D-Ala2-Met-enkephalinamide.
Assuntos
Analgesia , Endorfinas/farmacologia , Encefalina Metionina/análogos & derivados , Encefalinas/farmacologia , Movimento/efeitos dos fármacos , Taurina/farmacologia , Ácido gama-Aminobutírico/farmacologia , Animais , Relação Dose-Resposta a Droga , Cinética , Leucina/farmacologia , Masculino , RatosRESUMO
Neurobehavioral effects of neurotensin and structural analogues in which tyrosine in position 11 was replaced by either its d-isomer [D-Tyr11]-NT, phenylalanine [Phe11]-NT or D-phenylalanine [D-Phe11]-NT were studied. Results demonstrate that whereas neurotensin and [Phe11]-NT significantly decreased motor activity in rats, [D-Tyr11]-NT and [D-Phe11]-NT produced a marked and significant increase in activity. Such dichotomous action between analogues was not found for the hypothermic and muscular relaxation effects of neurotensin.
Assuntos
Atividade Motora/efeitos dos fármacos , Neurotensina/análogos & derivados , Neurotensina/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Isomerismo , Masculino , Relaxamento Muscular/efeitos dos fármacos , Ratos , Relação Estrutura-AtividadeRESUMO
Locomotor activity and grooming behavior of rats were recorded for a period of 30 min following intraventricular injections of substance P(SP) in doses of 0.60 and 2.50 microgram/rat. The lower dose of the peptide significantly increased locomotion for 10 min and time spent grooming for 25 min. The effects of the same two doses of SP on the hypokinesia induced by various pharmacological treatments modifying catecholaminergic systems were then examined. SP did not affect the behavioral depression produced by alpha-methyl-para-tyrosine (250 mg/kg), FLA-63 (25 mg/kg) and phenoxybenzamine (20 mg/kg). However, SP, in dose of 0.60 microgram/rat, systematically reversed the decrease in locomotor activity induced by a relatively small dose of haloperidol, 0.1 mg/kg. The dame dose of the peptide significantly counteracted the rigidity but not the hypokinesia and catalepsy resulting from the previous administration of a higher dose of haloperidol, 3 mg/kg. The results support the hypothesis that SP may exert direct or indirect function in motor behavior, possible via a modulatory action on brain dopaminergic systems.
Assuntos
Comportamento Animal/efeitos dos fármacos , Haloperidol/farmacologia , Atividade Motora/efeitos dos fármacos , Substância P/farmacologia , Animais , Dissulfeto de Bis(4-Metil-1-Homopiperaziniltiocarbonila)/farmacologia , Locomoção/efeitos dos fármacos , Metiltirosinas/farmacologia , Fenoxibenzamina/farmacologia , Ratos , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , alfa-MetiltirosinaRESUMO
We have demonstrated that injection of manganese into one caudate nucleus in rats results in a predominant ipsilateral turning behavior, accompanied at higher doses by an intermittent, alternating and dose-related incidence of contralateral turning and stereotypies. Although the pharmacological evidence produced (effect of alpha-MT, L-DOPA, pargyline) indicates a definite participation of the dopaminergic system in the latter two phenomena, it is probable that ipsilateral turning is the result of involvement of other transmitter systems as well. Tegmental serotoninergic and intrastriatal cholinergic pathways appear to be involved in the production of the basic postural asymmetry resulting in turning. The amount of interference with the nigrostriatal and mesolimbic dopaminergic pathways may determine the speed of circling, and the concurrent inhibition of locomotion. This is more evident with bilateral injections. Manganese appears to act at presynaptic levels within the striatum by blocking release of the transmitter, thus creating a localized, relative deficit in caudate function. The end result is the release of the dominant "ipsilateral syndrome-inducing system' from its inhibitory control. Repeated or chronic administration of this metal in man or animals is known to result in a brain dopamine and/or serotonin deficit commensurate with the clinical manifestations of bradykinesia and dystonia. Our results are compatible with the anatomical findings of Poirier and collaborators and tend to support the dual ipsilateral and contralateral syndrome-inducing systems in the caudate postulated by Cools, and the complementary roles of dopamine, serotonin and acetylcholine within that nucleus. No one transmitter is involved alone in the experimental production of the manganese syndrome, or of its component symptoms.
Assuntos
Comportamento Animal/efeitos dos fármacos , Núcleo Caudado/efeitos dos fármacos , Manganês/farmacologia , Atividade Motora/efeitos dos fármacos , Agressão/efeitos dos fármacos , Animais , Benserazida/farmacologia , Cloreto de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Hidroxidopaminas/farmacologia , Levodopa/farmacologia , Masculino , Metiltirosinas/farmacologia , Pargilina/farmacologia , Ratos , Fatores de TempoRESUMO
We have evaluated the cardiovascular effects of intracerebroventricular (i.c.v.) injections of neurotensin (NT) in pentobarbital-anesthetized rats. In most animals, the i.c.v. injection of NT (5.4, 10.8 and 16.2 nmol/rat) induced a dose-dependent fall of the arterial blood pressure. This effect was usually rapid in onset (30-60 sec) and of short duration (approximately 1-4 min). It was not preceded nor accompanied by any significant alteration of the heart rate. In about 25% of the animals, the vasodepressor effect of i.c.v. injections of NT was long lasting (30-45 min). Conscious rats were much less sensitive than anesthetized animals. The hypotensive effects of intravenously (i.v.) administered NT was fully maintained in animals made tolerant to the hypotensive effect of centrally administered NT. Similarly, the animals made unresponsive to i.v. injections of NT either by repeated i.v. injections of NT (e.g. tachyphylaxis) or by a chronic treatment with compound 48/80, still responded normally to centrally administered NT. The results suggest the existence of at least two anatomically distinct sites of action through which NT can induce hypotension in rats. One appears to be located in the periphery and the other, in the central nervous system.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Neurotensina/farmacologia , Animais , Tolerância a Medicamentos , Injeções Intraventriculares , Masculino , Neurotensina/administração & dosagem , Ratos , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
Effects of taurine on tolerance to [D-Ala2, Met5]enkephalinamide (DAME) were investigated in rats. Tolerance was produced by five intraventricular administrations of DAME (50 microgram) during 3 consecutive days. The magnitude of developed tolerance to DAME was not uniform for each behavioral parameter; tolerance to analgesia effects developed more intensively and rapidly from the repeated injections of the peptide than that to akinesia effects. Pretreatment with taurine (9.5 X 10(-2) M) which was injected in a volume of 10 microliter intraventricularly 10 min prior to every administration of DAME suppressed the development of tolerance to both analgesia and akinesia effects of this peptide, whereas pretreatment with L-leucine at the same concentration did not. Spontaneous locomotor activity was measured for 1 h after the 90-min behavioral observation period was completed. That activity increased with the number of the peptide injections. Taurine pretreatment inhibited the induction of 'hyper'-locomotor activity. These results support the view that taurine may possess an ability to inhibit development of tolerance to morphine-like peptides in rats.
Assuntos
Encefalina Metionina/análogos & derivados , Taurina/farmacologia , Analgesia , Animais , Comportamento Animal/efeitos dos fármacos , Tolerância a Medicamentos , Encefalina Metionina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
1. Sub-microgram levels of dopamine (DA), noradrenaline (NA) and serotonin (5HT) were estimated simultaneously in small discrete areas of brain by a simple combined alumina adsorption-spectrofluorometric technique. 2. The method does not depend on the use of ninhydrin which is reported to interfere with the spectrofluorometric assay of 5HT nor does the method involve the use of phosphate buffers which reportedly are a source of error in catecholamine assays. 3. The method described is suitable for the measurement of amine levels both in normal conditions and when amino levels have been severly reduced by amine-depleting drugs. Neither reserpine nor alpha-methyl-p-tyrosine interfere in the assay.
Assuntos
Química Encefálica , Dopamina/análise , Norepinefrina/análise , Serotonina/análise , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Dopamina/metabolismo , Masculino , Metiltirosinas/farmacologia , Microquímica , Norepinefrina/metabolismo , Ratos , Reserpina/farmacologia , Serotonina/metabolismo , Espectrometria de Fluorescência/métodosRESUMO
The effect of 1-methyl-4-phenyl-pyridinium (MPP+), the main toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonism-causing neurotoxin, upon the activity of nicotinamide adenine dinucleotide (NADH) cytochrome c reductase (EC 1.6.99.3) and upon that of glutathione reductase (EC 1.6.4.2) was monitored spectrophotometrically. For the cytochrome c reductase, the increase in absorbance of reduced cytochrome c was measured at 550 nm; for evaluating glutathione reductase, the absorbance of nicotinamide adenine dinucleotide phosphate (NADPH) was followed at 340 nm. MPP+ but not MPTP reversibly inhibited NADH cytochrome c reductase, but not glutathione reductase. This may be a direct mechanism of cell toxicity by this neurotoxin.
Assuntos
Redutases do Citocromo/antagonistas & inibidores , NADH Desidrogenase/antagonistas & inibidores , Compostos de Piridínio/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , 1-Metil-4-fenilpiridínio , Animais , Glutationa Redutase/metabolismo , Doença de Parkinson Secundária/induzido quimicamente , Piridinas/metabolismo , Piridinas/farmacologia , Compostos de Piridínio/metabolismo , EspectrofotometriaRESUMO
Three groups have reported defective antioxidant mechanisms in substantia nigra of patients with Parkinson's disease, namely a decreased catalase and peroxidase activity, a reduction of glutathione and, more recently, a diminished nigral glutathione peroxidase activity. We decided to investigate these mechanisms in erythrocytes to determine whether these brain defects represent generalized or genetic aberrations, in which case they should also be present in blood cells. The glutathione cycle has been investigated (reduced and oxidized glutathione, glutathione reductase and peroxidase) plus the activities of catalase and superoxide dismutase. The basal malonaldehyde content of erythrocytes was used as an index of endogenous lipid peroxidation. None of the above-mentioned parameters were found altered in erythrocytes of parkinsonians, suggesting that no genetic or generalized biochemical abnormalities underly the deficiencies detected in substantia nigra.
Assuntos
Eritrócitos/metabolismo , Doença de Parkinson/sangue , Glutationa/sangue , Humanos , Oxirredução , Substância Negra/metabolismoRESUMO
Veratramine produces a characteristic excitatory action on the central nervous system, producing both tremor and a characteristic "struggling" behavior. This behavioral excitation is accompanied by changes in serotonin content in hypothalamus. The central serotonin agonist methysergide in doses of 5--15 mg per kg produces a dose-dependent inhibition of veratramine's action, while parachlorophenylalanine has no effect. These results are consistent with a serotonin agonist mechanism to explain veratramine's action.
Assuntos
Receptores de Serotonina/efeitos dos fármacos , Serotonina/metabolismo , Alcaloides de Veratrum/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Glutamato Descarboxilase/metabolismo , Masculino , Metisergida/farmacologia , Camundongos , Atividade Motora/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
Pathological and biochemical evidence reviewed favours the hypothesis that the dementia seen in Parkinson's disease, particularly after long-term levodopa therapy, is akin to Alzheimer's disease. We postulate, in late Parkinson's disease, the development of a relative cholinergic deficiency due to the accelerated process of aging and the presence of neurofibrillary tangles (with choline acetyl transferase deficiency.) This process would be enhanced by the imbalance in favour of dopaminergic predominance caused by chronic levodopa therapy, and would partially explain the increase in dementia. As a test of this hypothesis we have given 10 levodopa-treated parkinsonian patients with dementia, a regimen of lecithin (average 20 gms/day). A clear improvement in Kohs block design test of constructive ability was noted with a decrease in the toxic symptoms of confusion, hallucinations and nightmares. In another study lecithin produced a decrease in levodopa-induced abnormal movements, but at the expense of motor performance. These preliminary investigations indicate that the progressive dementia of Parkinson's disease may not be irreversible.
Assuntos
Doença de Parkinson/tratamento farmacológico , Fosfatidilcolinas/uso terapêutico , Humanos , Testes de Inteligência , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologiaRESUMO
In this essay we first review the important contributions of Dr. George Cotzias to the understanding of chronic manganese intoxication and of manganese metabolism in man and animals. We also indicate the original contribution of Dr. John Donaldson to the mechanism of the neurotoxicity of manganese. In a second phase, the author challenges the tenet that Parkinson's disease is a form of chronic manganese intoxication and that manganism is an experimental model for Parkinson's disease. Clinical, pathological, experimental and biochemical evidence are brought to bear on this argument. Thirdly the author proposes that the necessary event to the so-called "depigmentation" of the substantia nigra and subsequent bradykinetic "low dopamine" syndrome is an early enhanced turnover of dopamine. Manganese intoxication is only one of the factors which may serve as a trigger to this event. Many others are also listed. In opposition to current views, who look for causal factors in Parkinson's disease along the pathways for melanogenesis, the author thus proposes a novel hypothesis which envisions a variety of transient "trigger factors" acting at the dopamine synapse to increase dopamine turnover. In turn, this increased synthesis of dopamine favours the production of large quantities of free radicals within the cell bodies in the substantia nigra, eventually overflowing the scavenging capacity of neuromelanin and their protective barrier, and causing cell death. The resulting decreased pool of dopamine-producing cells leads to a self-perpetuating situation of ever increasing demand on the remaining cells, and "progression" of the disease. Finally the author stresses the fact that genetic factors may play a role in an individual's susceptibility to such triggers. Again defective manganese transport, metabolism or binding are only some of the mechanisms possibly underlying such genetic predisposition to induced basal ganglia disorders. Further studies relating to manganese in these disorders and particularly in Parkinson's disease should focus not on the "intoxication" part of the overload and its striatopallidal consequences, but on the intimate mechanism of destabilization of the homeostatic regulator in neuromelanin bearing cells, even after the exposure period.
Assuntos
Doenças dos Gânglios da Base/fisiopatologia , Manganês/fisiologia , Animais , Gânglios da Base/fisiologia , Química Encefálica/efeitos dos fármacos , Catecolaminas/metabolismo , Modelos Animais de Doenças , Humanos , Levodopa/farmacologia , Intoxicação por Manganês , Melaninas/fisiologia , Hormônios Estimuladores de Melanócitos/fisiologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Substância Negra/metabolismo , Substância Negra/fisiopatologiaRESUMO
We demonstrate that injections of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP), 1-methyl-4-phenyl-pyridinium ion (MPP+) and Paraquat (PQ+) produce in Rana Pipiens different behavioral, biochemical and skin pigmentation changes. MPTP causes in frogs the main symptoms of Parkinsonism (rigidity, akinesia and tremor) and it darkens the skin of animals. It also decreases brain and, less so, adrenal medulla dopamine. These effects are blocked by Pargyline. MPP+ causes the same symptoms but more rapidly. In contrast, skin pigmentation is clearly lightened. Brain and particularly adrenal dopamine reserves are nearly abolished. Pargyline increases these effects. Paraquat, in a cumulative fashion, eventually causes the same behavioral changes and a slight increase in pigmentation. It initially produces an increase in brain and adrenal dopamine concentrations, but later a significant dopamine concentration decrease. Pargyline potentiates these long term effects, blocks the dopamine increase, but reverses the PQ+ effect upon melanin, producing the same depigmentation as MPP+ alone.