MCI-9042: high affinity for serotonergic receptors as assessed by radioligand binding assay

J Pharmacobiodyn. 1991 Apr;14(4):177-81. doi: 10.1248/bpb1978.14.177.

Abstract

This study assessed the specificity of displacement potencies of MCI-9042 [+/-)-1-[o-[2-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)- 2-propyl hydrogen succinate hydrochloride), a new antiplatelet agent, in [3H]4-bromo-2,5-dimethoxyphenylisopropylamine [( 3H]DOB) and [3H]ketanserin binding to 5HT2-serotonergic receptors in the rat brain using the radioligand binding method. The assessment of the displacement potencies of MCI-9042 and its derivative, M-1 [(+/-)-1-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)- 2-propanol)hydrochloride), on alpha 1-, alpha 2-, beta-adrenergic, 5HT1-, 5HT2- and muscarinic receptors were also studied. MCI-9042 and M-1 showed strong displacement effects to 5HT2-receptors using [3H]DOB binding and [3H]ketanserin binding sites, and weak displacement effects for [3H]serotonin, [3H]prazosin, [3H]p-aminoclonidine, [3H]CGP12177 and [3H]QNB binding to 5HT1-, alpha 1-, alpha 2-, beta-adrenergic receptors and muscarinic receptors. Thus, the present study suggests that MCI-9042 is specific for 5HT2-receptor.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Binding, Competitive
  • Brain Chemistry / drug effects
  • Clonidine / analogs & derivatives
  • Clonidine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Kinetics
  • Platelet Aggregation Inhibitors / pharmacology*
  • Prazosin / pharmacology
  • Propanolamines / pharmacology
  • Radioligand Assay
  • Rats
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Muscarinic / drug effects
  • Receptors, Serotonin / drug effects*
  • Succinates / pharmacology*

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic beta-Antagonists
  • Platelet Aggregation Inhibitors
  • Propanolamines
  • Receptors, Adrenergic, alpha
  • Receptors, Adrenergic, beta
  • Receptors, Muscarinic
  • Receptors, Serotonin
  • Succinates
  • sarpogrelate
  • apraclonidine
  • Ketanserin
  • Clonidine
  • CGP 12177
  • Prazosin