The partial DA receptor agonist
preclamol, (-)-3-PPP (50-200 mumol/kg, s.c.) partially reversed the
catalepsy induced by the
dopamine (DA) receptor antagonists
haloperidol (5.3 mumol/kg, i.p.) and
raclopride (20.1 mumol/kg, i.p.) in rats.
Terguride (
transdihydrolisuride), a partial DA receptor agonist with an efficacy lower than that of
preclamol, blocked
haloperidol (10.6 mumol/kg, i.p.) induced
catalepsy at 5 mumol/kg, s.c., but not at 20 mumol/kg, s.c. The effects of
terguride in this assay are possibly related to the compound's mixed partial DA agonist/
5-HT1A receptor agonist properties. The high efficacy agonist,
pramipexole (
SND 919) also blocked
haloperidol induced
catalepsy at 50 mumol/kg, s.c.
Haloperidol (0.33-1.3 mumol/kg, i.p.) reduced the locomotor activity down to 5% of saline controls and elevated limbic and striatal
DOPA accumulation. When combined with
haloperidol,
preclamol (100-200 mumol/kg, s.c.) antagonized both the strong hypomotility and increase in
DOPA accumulation. Finally, the elevation of serum
prolactin in rats induced by
haloperidol (0.25 mumol/kg, i.p.) was significantly antagonized by co-administration of
preclamol (39 mumol/kg, s.c.). These results show that partial DA agonists can reverse both behavioral, biochemical and neuroendocrine effects of
neuroleptics. It also suggests the utility of partial DA receptor agonists in combination with classical
neuroleptics in order to minimize the appearance of extrapyramidal side-effects and
hyperprolactinemia.