[125]I-spectramide: a novel benzamide displaying potent and selective effects at the D2 dopamine receptor.
The new substituted benzamide Spectramide, (N-[2-[4-iodobenzyl-N-methylamino]-2-methoxy-4-ethyl]-5-chloro- methylamine] benzamide) labelled with 125I was used as a potent and highly selective dopamine-D2 receptor antagonist in rat striatal homogenates for in vitro receptor binding. Kinetic experiments demonstrated the reversibility of the binding and the estimated Kd from saturation analysis was 25 pM, with a Bmax of 20 pmol/g of tissue. Competition studies showed that spectramide did not interact potently with the D1 or dopamine-uptake site. Drugs known to interact with other receptor systems were weak competitors of the binding, while binding was potently inhibited by other D2 antagonists, such as spiperone and eticlopride. These data indicate that Spectramide binds selectively and with high affinity to the dopamine D2 receptors, and may prove to be a useful tool for the study of these receptors in vivo using PET or SPECT.
Sánchez-Roa
P M
PM
NIDA Addiction Research Center, Baltimore, MD 21224.
Grigoriadis
D E
DE
Wilson
A A
AA
Sharkey
J
J
Dannals
R F
RF
Villemagne
V L
VL
Wong
D F
DF
Wagner
H N
HN
Kuhar
M J
MJ
D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism / Q000494:pharmacology
D001549:Benzamides; D001552:Benzazepines; D018492:Dopamine Antagonists; D007457:Iodine Radioisotopes; D010879:Piperazines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C060906:spectramide; D013134:Spiperone; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine