ABSTRACT
Marked, disabling fluctuations in motor performance (on-off phenomena) appear after chronic L-Dopa therapy in Parkinson's disease (PD). Intravenous infusion of L-Dopa greatly reduces these motor fluctuations, but it is not reliable as a chronic treatment. Therefore, infusion of the potent, water-soluble dopaminergic agonist lisuride has been tested. However, many patients did not respond to infusion of lisuride alone, and no clinical parameter is known to correlate with the lacking response. In order to study this problem, we performed the TRH test (200 micrograms i.v.) in 8 PD patients with severe motor fluctuations; before and during lisuride subcutaneous infusion, we measured PRL and TSH responses to TRH. Both PRL and TSH receive an inhibitory control from dopaminergic receptors on pituitary cells, whereas they are stimulated by TRH. The TRH test, given during lisuride infusion, allows an indirect evaluation of the 'brake function' of the dopaminergic system on anterior pituitary, i.e. of dopaminergic receptor sensitivity in vivo. In our study, TRH induced a significant TSH rise in all PD patients, before and during lisuride infusion. Moreover, the lisuride responders (i.e. patients showing constant 'on' period during lisuride infusion, 4 patients) showed a significant lower TSH response as compared to nonresponders. PRL levels followed the same trend without reaching statistical significance. These data are compatible with the presence, in the two groups, of a different pituitary dopaminergic sensitivity which would suggest the presence of pharmacodynamic factors associated with the lacking response to intravenous lisuride infusion.
Subject(s)
Lisuride/administration & dosage , Motor Skills/drug effects , Neurologic Examination , Parkinson Disease/drug therapy , Prolactin/blood , Receptors, Dopamine/drug effects , Thyrotropin-Releasing Hormone , Thyrotropin/blood , Antiparkinson Agents/administration & dosage , Drug Therapy, Combination , Female , Humans , Infusion Pumps , Levodopa/administration & dosage , Male , Motor Skills/physiology , Parkinson Disease/blood , Receptors, Dopamine/physiologyABSTRACT
Setoperone (R 52245), a serotonin S2 and dopamine D2 receptor blocker, was tested on eight healthy male volunteers, receiving 5 or 40 mg orally, in order to assess the modifications of plasma prolactin levels, as an index of receptor blocking activity. Both doses significantly increased plasma levels, confirming the dopamine blocking activity. In vitro and in vivo studies have shown serotonin S2 receptor blockade and lysergic acid diethylamide antagonist activity. Setoperone is proposed as a possible new neuroleptic drug.
Subject(s)
Antipsychotic Agents/pharmacology , Prolactin/blood , Pyrimidinones/pharmacology , Adolescent , Adult , Dopamine Antagonists , Humans , Male , Receptors, Serotonin/metabolismABSTRACT
A double-blind crossover trial was carried out on the sleep-inducing activity of a new preparation (oral drops) of lormetazepam versus placebo. Twenty patients were included and requested to subjectively evaluate their sleep, both by analogue scales and semiquantitative ratings, during 2-night administration of the two products. Also, the usual parameters, sleep duration, sleep latency and number of awakenings were evaluated. Lormetazepam drops appeared to exert the same actions as the capsules' preparation, being significantly different from those of the placebo.
