The dopamine autoreceptor agonist, (+/-)-trans-1,3,4,4a5,10b-hexahydro-4-propyl-2H [1]benzopyrano [3,4-b] pyridin-9-ol hydrochloride (CGS 15855A), modulates striatal dopamine metabolism and prolactin release.
The effects of apomorphine and the putative dopamine autoreceptor agonist, CGS 15855A, were evaluated in several functional assays that are modulated by pre- or post-synaptic D2 receptors. These included release of prolactin in vivo and in vitro from cultured lactotrophs; levels of dihydroxyphenylacetic acid (DOPAC) in the striatum; levels of acetylcholine (ACh); in the striatum and concentrations of cyclic guanosine monophosphate (cyclic GMP) in the cerebellum. The secretion of prolactin was inhibited by CGS 15855A in vitro and in vivo and which also decreased the levels of DOPAC in the striatum at doses 5-25 times less than those required to increase ACh in the striatum and levels of cGMP in the cerebellum. In contrast, apomorphine possessed a dose-ratio between 1.5 and 8.6 for these assay systems. These data suggest that CGS 15855A is a selective dopamine autoreceptor agonist which preferentially stimulates D2 receptors on lactotrophs and dopaminergic neurons as compared to D2 receptors on cholinergic interneurons in the striatum.
Iyengar
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S
Research Dept., CIBA-GEIGY Corp., Summit, New Jersey 07901.
Hausler
A
A
Kim
H S
HS
Marien
M
M
Altar
C A
CA
Wood
P L
PL
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2
D001578:Benzopyrans; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C051347:CGS 15855A; D011388:Prolactin; D001058:Apomorphine; D004298:Dopamine