Comparison of the effects of recently developed alpha 2-adrenergic antagonists with yohimbine and rauwolscine on monoamine synthesis in rat brain.
The effects of two recently developed alpha 2-adrenergic antagonists, RX 781094 and WY 26703, on the synthesis of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in rat brain were compared to those of yohimbine, its diastereoisomer rauwolscine, and mianserin. Intraperitoneal administration of these compounds increased cortical NE synthesis with the potency order: yohimbine, RX 781094, WY 26703 greater than rauwolscine greater than mianserin. Within a similar dose range, yohimbine, rauwolscine and WY 26703 also stimulated striatal DA synthesis and decreased hypothalamic 5-HT synthesis, while RX 781094 and mianserin were very weak or inactive. Yohimbine and the structurally-related WY 26703 were also active as DA antagonists in the gamma-butyrolactone model for DA autoreceptor function. Based on the drug-induced changes in monoamine synthesis as indication of receptor-mediated events, RX 781094 has greater selectivity as an alpha 2-antagonist than compounds structurally related to yohimbine.
Pettibone
D J
DJ
Pfleuger
A B
AB
Totaro
J A
JA
D015107:4-Butyrolactone / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000096:biosynthesis*; D001921:Brain / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D009638:Norepinephrine / Q000096:biosynthesis; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001679:Biogenic Amines; D004146:Dioxanes; D011807:Quinolizines; D008803:Mianserin; D015016:Yohimbine; D012701:Serotonin; D004295:Dihydroxyphenylalanine; C038538:Wy 26703; D015107:4-Butyrolactone; D009638:Norepinephrine; D019329:Idazoxan