Paraxanthine displaces the binding of [3H]SCH 23390 from rat striatal membranes.
We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 microM; K(low) = 95.9 microM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 microM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 microM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioural stimulation produced by caffeine.
Laboratori de Neuropsicofarmacologia (Programa Sant Pau-CITRAN, Fundació d'Investigació Santa Creu i Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
S
S
Ferré
T
T
Guix
J
J
Sallés
A
A
Badia
P
P
Parra
F
F
Jané
M
M
Herrera-Marschitz
U
U
Ungerstedt
M
M
Casas
D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism; D013806:Theophylline / Q000378:metabolism*
D001552:Benzazepines; D011954:Receptors, Dopamine; D006165:Guanylyl Imidodiphosphate; D002110:Caffeine; D013134:Spiperone; D013806:Theophylline; C021183:1,7-dimethylxanthine