The behavioural effects of
CM 30366, an
aminopyridazine derivative, on
dopamine-mediated neurotransmissions, have been studied in mice and rats.
CM 30366 induced stereotyped behaviour and antagonized
haloperidol-induced
catalepsy in rats, after parenteral and
oral administration. In 6-hydroxy
dopamine (6-OHDA)-lesioned mice,
CM 30366 induced contralateral rotations and, when injected before
6-OHDA, protected mice against its neurotoxicity.
CM 30366 also provoked contralateral rotations when injected directly into the mouse right striatum. After parenteral injection,
CM 30366 slightly increased motility in mice, at least at low doses. The stereotypies and rotations (after intrastriatal injection) induced by
CM 30366 were antagonized by
haloperidol,
alpha-methyl-p-tyrosine and
reserpine. The effects of
CM 30366 were compared to those of direct and indirect
dopamine-like drugs.
Bromocriptine induced a behavioural profile, which in most aspects, was qualitatively and quantitatively similar to that of
CM 30366.
Apomorphine was found slightly more potent than
CM 30366, but in contrast to the latter,
apomorphine-induced stereotypies were insensitive to
alpha-methyl-p-tyrosine or
reserpine. (+)-
Amphetamine and
nomifensine were less potent than
CM 30366, and unlike
CM 30366, induced ipsilateral rotations in 6-OHDA-lesioned mice. These results indicate that
CM 30366 is a potent atypical
dopamine-like
drug of potential therapeutic usefulness.