MCI-9042: high affinity for serotonergic receptors as assessed by radioligand binding assay.
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.
Maruyama
K
K
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Kinami
J
J
Sugita
Y
Y
Takada
Y
Y
Sugiyama
E
E
Tsuchihashi
H
H
Nagatomo
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D007700:Kinetics; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D013386:Succinates / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D010975:Platelet Aggregation Inhibitors; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D013386:Succinates; C064294:sarpogrelate; C016986:apraclonidine; D007650:Ketanserin; D003000:Clonidine; C033394:CGP 12177; D011224:Prazosin