RESUMO
This randomized, double-blind trial was designed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from off to on state after single intravenous infusion. Ten fluctuating patients with idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2-16 mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the motor deficit (UPDRS, motor score) including akinesia at the first evaluation time point of 15 minutes, and in reversing off state of 7 of 10 patients. The doses were equally effective, although the effect was more sustained with the highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil were not correlated to the motor score improvement or switch from off-->on. In conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and effective in improving motor symptoms, including akinesia, of fluctuating PD patients.
Assuntos
Agonistas de Dopamina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Piribedil/uso terapêutico , Idoso , Agonistas de Dopamina/sangue , Relação Dose-Resposta a Droga , Avaliação de Medicamentos/métodos , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Piribedil/sangue , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of the present study was to compare, in chloral-hydrate anaesthetized rats, the alpha(2)-adrenergic properties of the selective 5-HT(1A) receptor agonist, alnespirone (S-20499), with those of buspirone, a 5-HT(1A) receptor agonist exhibiting potent alpha(2)-adrenoceptor antagonist properties via its principal metabolite, 1-(2-pyrimidinyl)-piperazine. Both locus coeruleus spontaneous firing activity and noradrenaline release in the medial prefrontal cortex were potently inhibited by the alpha(2)-adrenoceptor agonist clonidine, at a dose of 40 microg/kg (i.p.). Such an inhibition was neither prevented nor reversed by alnespirone (10 mg/kg, i.p.), while buspirone, at the same dose, potently antagonized the locus coeruleus inhibitory effects of clonidine. These data demonstrate that, in contrast with some aryl-piperazine compounds (such as buspirone), alnespirone, either on its own or via a possible metabolite such as buspirone, is devoid in vivo of significant alpha(2)-adrenoceptor antagonist properties.