Intravenous and intraduodenal injection of a new
ergoline derivative,
TL-350, produced dose-dependent inhibition of heart rate increase produced by cardioaccelerator nerve stimulation in anesthetized cats. ID50 values of
TL-350 were 0.019 and 0.047 mumol/kg after i.v. and intraduodenal injection, respectively. This inhibition was reversed by either
sulpiride (0.15 mumol/kg i.v.) or
haloperidol (0.13 mumol/kg i.v.) but not by
yohimbine (0.14 mumol/kg i.v.).
TL-350 did not change
isoproterenol-induced
tachycardia and hypotensive responses.
TL-350 caused dose-dependent decrease of arterial blood pressure and heart rate in anesthetized cats.
Haloperidol (0.13 mumol/kg i.v.) prevented the hypotensive and bradycardic effects of the compound.
TL-350 also produced concentration-dependent inhibition of heart rate responses to transmural stimulation of isolated cat right atria. IC50 value was 0.026 microM.
Dopaminergic antagonists,
haloperidol and
sulpiride, antagonized the inhibitory effect of
TL-350 in in vitro experiments.
TL-350 did not stimulate presynaptic
alpha-2 adrenergic receptors in rat vas deferens and guinea-pig ileum.
TL-350 induced rotation for 3 hr in rats with unilateral denervated caudate nucleus. The compound was 0.5 as potent as
apomorphine. In [3H]
dopamine binding assays using rat caudate tissue,
TL-350 had approximately the same activity as
apomorphine in displacing the radioligand. It was concluded that
TL-350 is a selective
dopamine receptor agonist without possessing alpha and
beta adrenergic receptor stimulating activity.