Quantitative autoradiographic characterisation of the binding of [3H]WAY-100635, a selective 5-HT1A receptor antagonist.
The binding characteristics of [3H]WAY-100635 ([O-methyl 3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide trihydrochloride), a potent and selective 5-HT1A antagonist radioligand, were examined in the rat brain using in vitro quantitative receptor autoradiography. The regional distribution of specific [3H]WAY-100635 binding sites was heterogeneous and demonstrated a strong correlation with that of [3H]8-OH-DPAT binding. The highest concentrations of [3H]WAY-100635-labelled sites were found in the lateral septal areas, dorsal raphe n., entorhinal cortex and the hippocampal formation (CA1, CA3 and dentate gyrus). Scatchard transformation of saturation isotherms revealed saturable [3H]WAY-100635 binding sites of high-affinity: in the hippocampal formation, Kd was approximately 1 nM and Bmax ranged between 187 and 243 fmol/mg tissue wet weight, in the entorhinal cortex, Kd = 0.44 nM and Bmax = 194 fmol/mg tissue wet weight, and in the rostral portion of the dorsal raphe n., Kd = 0.52 nM and Bmax = 157 fmol/mg tissue wet weight. The affinity of [3H]WAY-100635 for the 5-HT1A binding site tended to be higher in the dorsal raphe n. and entorhinal cortex compared with that of the hippocampal formation. In contrast, the binding affinity of [3H]8-OH-DPAT in the hippocampal formation was between 1.1 and 2.3 nM and the Bmax was 137 to 183 fmoles/mg tissue wet weight; in the entorhinal cortex, Kd = 3.2 nM and Bmax = 141 fmoles/mg tissue wet weight, and in the rostral portion of the dorsal raphe n., Kd = 3.4 nM and Bmax = 163 fmol/mg tissue wet weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Khawaja
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Department of Molecular Pharmacology, Wyeth Research, Berkshire, UK.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain; D006624:Hippocampus; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors
D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin