The semisynthetic
lisuride derivative
transdihydrolisuride (
terguride, TDHL) is an effective antiparkinsonian
drug. In animals, TDHL appears to possess mixed
dopamine agonist-antagonist effects, but this may not be the case in man. Single doses of TDHL were given to 21 subjects with
parkinsonism. Overall, TDHL 0.25-0.5 mg caused dose-related improvement in
parkinsonism for periods of up to 6 h, although 8 of 21 subjects showed no improvement or deterioration with TDHL 0.5-1 mg. In three patients with
levodopa-induced
psychosis, the addition of TDHL 0.75 mg daily for 5-10 days did not alter the psychotic state. In three subjects with
levodopa-induced
dyskinesias, the addition of TDHL 0.75 mg daily for 14 days resulted in a slight increase in the severity of
involuntary movements. Side-effects of TDHL, sickness and
hypotension, were similar to those observed with
levodopa.
Transdihydrolisuride caused prolonged inhibition of
prolactin release, but unlike
levodopa did not elevate plasma
growth hormone levels. Additionally, TDHL did cause considerable sedation. These results may be due to combined effects of TDHL on nondopamine as well as
dopamine neurotransmitter systems, rather than to partial or incomplete
dopamine agonist effects.