In:
Journal of Pharmacy and Pharmacology, Oxford University Press (OUP), Vol. 54, No. 8 ( 2010-02-18), p. 1123-1128
Abstract:
The purpose of this study was to investigate the association and dissociation kinetics of [3H]AT-1015 from 5-HT2 receptors in rabbit cerebral cortex membranes using a radioligand binding assay method and to make a comparison with those of [3H] ketanserin binding. Scatchard analysis of [3H]AT-1015 binding in rabbit cerebral cortex membranes indicated the existence of a single class of binding sites (dissociation constant, Kd = 2.18 nm). The specific binding of [3H] AT-1015 increased slowly with time and the association rate constant of [3H] AT-1015 binding (k1 = 0.1229 min−1 nm−1) was two times slower than that of [3H]ketanserin binding (k1 = 0.2451 min−1 nm−1). The dissociation rate constant of [3H] AT-1015 binding (t1/2 = 37.03 min) was six times slower than that of [3H]ketanserin binding (t1/2 = 6.29 min), when the addition of excess unlabelled ligands were AT-1015 and ketanserin, respectively. The dissociation rate constant of [3H] AT-1015 was slowed to a greater degree (t1/2 = 163.40 min and t1/2 = 198.12 min) by the addition of ketanserin and sarpogrelate as excess unlabelled ligands than was that of [3H]ketanserin (t1/2. = 17.76 min and t1/2. = 18.45 min) by the addition of AT-1015 and sarpogrelate as an excess unlabelled ligand, respectively. These findings on the dissociation kinetics of [3H] AT-1015 have confirmed and supported previously reported evidence of the slower dissociation of AT-1015 from 5-HT2 receptors.
Type of Medium:
Online Resource
ISSN:
0022-3573
,
2042-7158
DOI:
10.1211/002235702320266299
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2010
detail.hit.zdb_id:
2041988-0
detail.hit.zdb_id:
2050532-2
SSG:
15,3
Permalink