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A Search for New 5‐HT 1A /5‐HT 2A Receptor Ligands. In Vitro and in vivo Studies of 1‐[ω‐(4‐Aryl‐1‐piperazinyl)alkyl]indolin‐2(1 H )‐ones
Author(s) -
Mokrosz Maria J.,
Duszyńska Beata,
Misztal Stanisław,
Kłodzińska Aleksandra,
Tatarczyńska Ewa,
ChojnackaWójcik Ewa,
DziedzickaWasylewska Marta
Publication year - 1998
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(199810)331:10<325::aid-ardp325>3.0.co;2-6
Subject(s) - 5 ht1a receptor , in vivo , chemistry , aryl , intrinsic activity , receptor , stereochemistry , 5 ht receptor , biological activity , in vitro , structure–activity relationship , lead compound , alkyl , serotonin , pharmacology , agonist , biochemistry , biology , organic chemistry , microbiology and biotechnology
A series of 1‐[ω‐(4‐aryl‐1‐piperazinyl)alkyl]indolin‐2(1 H )‐one derivatives 2–14 was synthesized in order to obtain ligands with a dual 5‐HT 1A /5‐HT 2A activity. The majority of those compounds ( 2–5, 7, 10–13 ) exhibited a high 5‐HT 1A ( K i = 2 – 44 nM) and/or 5‐HT 2A affinity ( K i = 51 and 39 for 5 and 7 , respectively). Induction of lower lip retraction (LLR) and behavioral syndrome and inhibition of these efects evoked by 8‐hydroxy‐2‐(di‐ n ‐propyl‐amino)tetralin (8‐OH‐DPAT) were used for determination the agonistic and antagonistic activity, respectively, at 5‐HT 1A receptors. The 5‐HT 2A antagonistic activity was assessed by the blocking effect on the head twitches induced by (±)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI) in mice. Two of the tested compounds, 1‐{3‐[4‐(3‐chlorophenyl)‐1‐piperazinyl]propyl}‐6‐fluoroindolin‐2(1 H )‐one ( 5 ) and 1‐{3‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]propyl}indolin‐2(1 H )‐one ( 7 ), demonstrated a high 5‐HT 1A /5‐HT 2A affinity and an in vivo antagonistic activity towards both receptor subtypes.