title: Inhibition of oestradiol-induced prolactin release in a dual-cannulated ovariectomized rat model by carmoxirole, a peripherally restricted dopamine agonist.
abstract: Centrally acting dopamine agonists (e.g. bromocriptine) and dopamine transport inhibitors (e.g. GBR12909) are known to inhibit oestradiol-induced prolactin release. The capacity of peripherally restricted compounds to do likewise, however, is unknown. Here, the effects of the peripherally restricted dopamine receptor agonist carmoxirole on oestradiol-induced prolactin release were investigated. Dual-cannulated ovariectomized rats were used, so that a robust, reproducible response to exogenous oestrogen could be induced and sequential blood samples were taken with minimal stress. Carmoxirole (15 mg/kg) inhibited oestradiol-induced prolactin release, similar to bromocriptine and GBR12909. However, carmoxirole also induced a rapid, transient, oestradiol-independent release of prolactin. These data show that peripherally restricted dopamine receptor agonists are sufficient to inhibit oestradiol-induced prolactin release. Like centrally acting compounds, they may therefore be expected to affect the incidence of prolactin-dependent tumours in rat carcinogenesis studies without inducing central-mediated side effects.
authors: Global Safety Assessment, AstraZeneca Pharmaceuticals, R&D, Wilmington, DE, USA. david.brott@astrazeneca.com
authors: David A
authors: DA
authors: Brott
authors: Jennifer L
authors: JL
authors: Werkheiser
authors: Pam
authors: P
authors: Campbell
authors: Patricia
authors: P
authors: Bentley
authors: Håkan H A S
authors: HH
authors: Andersson
authors: Jane
authors: J
authors: Stewart
authors: Russell
authors: R
authors: Huby
authors: Maneesha
authors: M
authors: Altekar
authors: Lewis B
authors: LB
authors: Kinter
mesh_terms: D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D010052:Ovariectomy; D010879:Piperazines / Q000494:pharmacology; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D018491:Dopamine Agonists; D004965:Estrogen Antagonists; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D001971:Bromocriptine; D004958:Estradiol; D011388:Prolactin; C043425:vanoxerine; C071485:carmoxirole