No abstract

Dopamine receptors in intracerebral motor and endocrine systems have been divided into two main types, D-1 and D-2, dependent on the presence or absence of adenylate cyclase linkage. Here we have investigated a number of dopamine agonist and antagonist drugs in man that have different actions on D-1 and D-2 receptors in animals. Motor and endocrine effects in parkinsonian subjects seem to depend on drug interaction with D-2, but not D-1, receptors. These results may have important implications for the design of anti-parkinsonian and antipsychotic agents.

The beta-carboline ZK 93,426, a benzodiazepine receptor antagonist, was administered intravenously to human volunteers at two different doses (0.01 mg/kg, 0.04 mg/kg) according to a double-blind, placebo controlled design. Vital functions (i.e. blood pressure, heart rate, ECG, EEG), peripheral (finger) skin temperature and performance in psychometric tests for psychotropic and cognitive effects were evaluated. Blood samples were collected in addition and certain pharmacokinetic parameters were estimated. ZK 93,426 in both doses was well tolerated and exhibited no side effects. A decrease in peripheral skin temperature and heart rate was observed. In a general estimation of behavioural changes, volunteers experienced a stimulant and activating effect of the drug. An improvement in performance was observed in two cognitive tasks, the "logical reasoning task" and "pictures differences task" which estimated concentration and attention, respectively. No effects were found in time estimation. Plasma levels 5 min after intravenous administration of ZK 93 426 were 16 +/- 10 ng/ml and 52 +/- 31 ng/ml for 0.01 mg/kg and 0.04 mg/kg, respectively. Total clearance was calculated as 46 +/- 22 ml/min/kg (0.04 mg/kg).

No link has been found between lisuride use and fibrotic cardiac valvulopathy, in agreement with the 5-HT(2B) receptor antagonist effect of this drug. The very low incidence of spontaneous reports of any other fibrosis could be even compatible with an association by chance in the population exposed to lisuride. Although close monitoring for this kind of side effects is still to be recommended in the therapy with lisuride, our data do not support the concept of a class effect suggesting that all ergot-derived drugs and especially DA receptor agonists with some chemical similarity to the ergot structure will cause or facilitate cardiac valvulopathies as observed with pergolide.

No abstract