Alkaloids from Eschscholzia californica and their capacity to inhibit binding of [3H]8-Hydroxy-2-(di-N-propylamino)tetralin to 5-HT1A receptors in Vitro.
A 70% ethanol extract of California poppy (Eschscholzia californica) was able to bind to 5-HT(1A) and 5-HT(7) receptors at 100 mug/mL. The subsequent isolation procedure yielded the known alkaloids californidine (1), escholtzine (2), N-methyllaurotetanine (3), caryachine (4), and O-methylcaryachine (5), along with a new pavine alkaloid, 6S,12S-neocaryachine-7-O-methyl ether N-metho salt (7). The structure of 7 was determined by spectroscopic data interpretation, while the absolute stereochemistry was determined by means of circular dichroism. From the results obtained from the radioligand-binding assay of the pure compounds, including the commercially available protopine (6), it was evident that the activity on the 5-HT(1A) receptor was at least partly due to the presence of the aporphine alkaloid 3, which showed the highest inhibition of [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) binding with an EC(50) value of 155 nM and a K(i) of 85 nM.
Gafner
Stefan
S
Tom's of Maine, 302 Lafayette Center, Kennebunk, Maine 04043, USA. stefang@tomsofmaine.com
Dietz
Birgit M
BM
McPhail
Kerry L
KL
Scott
Ian M
IM
Glinski
Jan A
JA
Russell
Fiona E
FE
McCollom
Megan M
MM
Budzinski
Jason W
JW
Foster
Brian C
BC
Bergeron
Chantal
C
Rhyu
Mee-Ra
MR
Bolton
Judy L
JL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D044182:Benzylisoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004149:Dioxoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D031675:Eschscholzia / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000470:Alkaloids; D044182:Benzylisoquinolines; D004149:Dioxoles; D017366:Serotonin Receptor Agonists; C510123:californidine; C510124:escholtzine; D044282:Receptor, Serotonin, 5-HT1A; C098741:caryachine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin