P Piccini

Diurnal motor variations to repeated doses of levodopa in Parkinson's disease

Patients with Parkinsons disease (PD) in long-term levodopa therapy often complain of worsening of motor symptoms in the afternoon and evening. The pathophysiology of this phenomenon is not known. We evaluated the motor response to repeated doses of levodopa during a 12-hour period in 52 parkinsonian patients (19 de novo, 20 stable, and 13 wearing-off). On the day of the study, all patients received standard doses of levodopa/carbidopa at 8:00 a.m., 12:00 noon, and 4:00 p.m. Motor measurements such as tapping test, walking time, and tremor score, and blood samples for levodopa and 3-O-methyldopa (3OMD) plasma analysis, were performed hourly. Mean motor scores and pharmacokinetic data, evaluated for a period of 3 hours after each levodopa dose, were compared. In de novo patients, we did not observe diurnal changes in motor score, whereas a progressive daytime worsening was visible in stable and wearing-off patients. No significant difference in levodopa pharmacokinetics after each levodopa dose was observed within each patient group, whereas 3OMD plasma levels significantly increased with repeated levodopa administrations. However, no significant correlation between motor scores and 3OMD plasma levels was observed, suggesting that the diminishing motor response to afternoon and evening doses of levodopa in patients in long-term levodopa therapy does not relate to the pharmacokinetics of the drug. It is possible that this phenomenon may be an expression of the occurrence of tolerance to repeated doses of levodopa.

Platelet monoamine oxidase B activity in parkinsonian patients.

Monoamine oxidase B (MAO B) plays a pivotal role in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonism. An increased MAO B activity in platelets of patients with idiopathic Parkinsons disease (PD) is reported in this study. The possibility that high MAO B activity may represent a trait of vulnerability for PD by enhancing the neurotoxic effects of environmental compounds is discussed.

Platelet peripheral benzodiazepine receptors are decreased in Parkinson's disease

Peripheral benzodiazepine (BDZ) receptors are located in a variety of tissues, including platelets, in the nuclear and/or mitochondrial membranes. We studied the density of peripheral BDZ receptors in platelets of 10 de novo Parkinsons disease (PD) patients, 18 PD patients treated with a levodopa/carbidopa combination, and in 15 healthy subjects matched for sex and age. The binding assay was conducted using [3H]PK 11195, a specific ligand for peripheral BDZ receptors. A significant decrease in the density of [3H]PK 11195 binding sites has been observed in PD patients with respect to controls (p less than 0.01), but not between de novo and treated PD patients. No correlation has been found between the decrease in density of [3H]PK 11195 binding sites in platelets and either the duration or severity of PD. Peripheral BDZ receptors are implicated in the regulation of mitochondrial respiratory function. Thus, their decrease in PD might parallel the abnormalities in mitochondrial function recently found in this neurologic disease.

Possible Involvement of Dopaminergic Mechanisms in the Antimigraine Action of Flunarizine

Flunarizine, a calcium antagonist widely used in the prophylactic treatment of migraine, may interfere with dopaminergic systems. Flunarizine therapy can in fact induce extrapyramidal side effects and can increase basal as well as stimulated prolactin levels. To better define the mechanism of flunarizine action in migraine, we studied prolactin and growth hormone responses to thyrotropin releasing hormone and sulpiride in 13 female migraineurs before and after 60 days of flunarizine therapy. The treatment did not modify basal prolactin and growth hormone levels, but prolactin response to thyrotropin releasing hormone was enhanced. A paradoxical increase of growth hormone to thyrotropin releasing hormone observed before therapy was blunted after flunarizine treatment. These data indicate a modulatory action of flunarizine on dopaminergic systems which might to some extent explain the antimigraine action of this drug.

Naloxone partly counteracts apomorphine side effects

The effects of naloxone on side effects provoked by apomorphine (APO) administration in patients with parkinsonian syndrome have been studied. The group under study included eight patients with Parkinsons disease and four with parkinsonism who received 100 micrograms/kg s.c. APO acutely to test dopaminergic responsiveness. All patients were treated with 20 mg domperidone tablets t.i.d. and then for 2 consecutive days (in double blind fashion) were given a 2-hour i.v. saline infusion alone or with naloxone (8 mg) starting 30 min before APO administration. In both groups, naloxone delayed the appearance of sleepiness, and reduced the intensity of yawning, sleepiness, nausea, and vomiting as compared with saline. These findings indicate a potential usefulness of naloxone and other opioid antagonists in preventing acute APO side effects.

Increased platelet 3H-imipramine binding and monoamine oxidase B activity in Alzheimer's disease.

SummarySeveral biochemical abnormalities in peripheral tissues have been reported in Alzheimers disease (AD).With this in mind we studied platelet monoamine oxidase B (MAO B) activity and 3H-imipramine (IMI) binding in both AD patients and healthy subjects and found a significantly higher level of platelet MAO B activity and 3 H-IMI Bmax values in the AD patients. In view of the part that MAO B plays in metabolizing serotonin (5 HT) and of the relationship which exists between 3 H-IMI binding and 5 HT uptake, our results would suggest that with AD there occurs a complex dysfunction in the 5 HT system, at least at a peripheral level.

Apomorphine in malignant syndrome due to levodopa withdrawal

We report a case of neuroleptic malignant syndrome (NMS) following abrupt reducation of chronic levodopa treatment in a 71 year old female parkinsonian patient. The NMS resolved within 24 hours of the addition of apomorphine to levodopa therapy.SommarioSi riporta un caso di sindrome maligna insorta in una donna di 71 anni affetta da morbo di Parkinson, dopo brusca riduzione della terapia cronica con levodopa e rapidamente risolta dal trattamento combinato con levodopa e apomorfina.

Transcranial Doppler Ultrasound in Migraine and Tension-Type Headache After Apomorphine Administration: Double-Blind Crossover Versus Placebo Study

The effect of the dopaminergic agonist apomorphine on blood velocity in the middle cerebral artery has been studied in patients with migraine, tension-type headaches, and healthy subjects by means of transcranial Doppler monitoring. Following the administration of apomorphine, systolic velocity and mean velocity significantly increased and pulsatility index significantly decreased in migraineurs compared to placebo and to the other groups of subjects. These changes were dose-dependent and showed a time-curve compatible with the pharmacokinetic profile of the drug. The different effect of apomorphine in migraineurs compared with controls and tension-type headache patients implies that migraineurs have increased sensitivity to dopaminergic stimuli and suggests that transcranial Doppler monitoring after apomorphine administration could be a useful tool in the evaluation of migraineurs.

Effect of naloxone on body temperature in postmenopausal women with Parkinson's disease

The role exerted by the endogenous opioid system on thermoregulation has been studied in six postmenopausal women affected by Parkinsons disease and in 6 age-matched, normal postmenopausal women, as controls. The women randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or of saline on two consecutive days. Body temperature, as evaluated by rectal temperature, was significantly lower (p less than 0.05) in Parkinsonian than in normal women, and it did not vary during saline infusion, in either groups. Naloxone infusion significantly reduced (p less than 0.01) body temperature in normal postmenopausal women, but it was unable to modify body temperature in women affected by Parkinsons disease. The low basal body temperature values and the inability of naloxone to exert a hypothermic effect in women suffering from Parkinsons disease seem to constitute further evidence for an impaired regulation of body temperature and impaired activity of the endogenous opioid system in this pathology.

Reduced luteinizing hormone secretion in women with Parkinson's disease.

SummaryPlasma luteinizing hormone (LH) levels were significantly lower in 10 postmenopausal women with Parkinsons disease (PD) compared to agematched controls. The remaining hypophyseal hormones and gonadal steroids were similar in PD patients and in controls, suggesting a selective alteration of hypothalamic dopaminergic mechanisms which regulate LH secretion.