ABSTRACT
The synthesis of a highly potent and selective NK1 receptor antagonist radioligand, [3H]-cis-3-[(2-methoxybenzyl)amino]-2-phenylpiperidine (6a) is described. The in vitro binding pharmacology and autoradiographic distribution of 6a in guinea pig brain following peripheral administration are also reported.
Subject(s)
Neurokinin A/antagonists & inhibitors , Neurokinin-1 Receptor Antagonists , Piperidines/chemical synthesis , Piperidines/pharmacology , Amino Acid Sequence , Animals , Autoradiography , Brain/metabolism , Guinea Pigs , Male , Molecular Sequence Data , Piperidines/metabolism , Radioligand Assay , Stereoisomerism , Substance P/chemistryABSTRACT
4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with this radioligand indicate that it effectively penetrates the blood-brain barrier upon peripheral administration. Thus, 5 should be a useful pharmacological tool for both in vitro and in vivo studies of this class of compounds.