Carmoxirole is able to reduce amisulpride-induced hyperprolactinemia without affecting its central effect.
Prolactin blood level and apomorphine-induced yawning were studied in rats treated with the substituted benzamide amisulpride in association with bromocriptine or carmoxirole; two dopamine D(2) receptor agonists with high or low propensity to cross the brain-blood barrier, respectively. Administration of amisulpride produced a maximum increase in rat serum prolactin level (315+/-18%) vs. vehicle-treated animals (ED(50)=0.25+/-0.017 mg/kg, s.c.). The concurrent administration of carmoxirole or bromocriptine completely reversed the hyperprolactinemia induced by amisulpride (0.5 mg/kg, s.c.) (ID(50)=14.9+/-0.8 mg/kg and 0.81+/-0.03 mg/kg, respectively). Carmoxirole (15 mg/kg, i.p.) did not affect yawning induced by apomorphine (0.08 mg/kg, s.c.) nor amisulpride (0.5 mg/kg, s.c.) blockade of apomorphine-induced yawning. Conversely, a significant increase in the number of yawns was observed when bromocriptine (0.8 mg/kg, i.p.) was associated with apomorphine in the absence or presence of amisulpride. These results suggested that a peripheral dopamine D(2) receptor agonists could be a useful tool in alleviating amisulpride-induced hyperprolactinemia without possibly affecting its central effect.
Marchese
Giorgio
G
Neuroscienze S.c.a.r.l., Cagliari, Italy.
Ruiu
Stefania
S
Casti
Paola
P
Bartholini
Francesco
F
Saba
Pierluigi
P
Gessa
Gian Luigi
GL
Pani
Luca
L
D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001667:Binding, Competitive; D001971:Bromocriptine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000188:drug therapy*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism / Q000648:ultrastructure; D011388:Prolactin / Q000097:blood; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism; D015000:Yawning / Q000187:drug effects
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D007211:Indoles; D011725:Pyridines; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D013469:Sulpiride; D000077582:Amisulpride; D011388:Prolactin; C071485:carmoxirole