In vitro and in vivo profile of SB 206553, a potent 5‐HT 2C /5‐HT 2B receptor antagonist with anxiolytic‐like properties

In vitro and in vivo profile of SB 206553, a potent 5‐HT 2C /5‐HT 2B receptor antagonist with... 1 SB 206553 (5‐methyl‐1‐(3‐pyridylcarbamoyl)‐1,2,3,5‐tetrahydropyrrolo(2,3‐f)indole) displays a high affinity (pK1 7.9) for the cloned human 5‐HT2C receptor expressed in HEK 293 cells and the 5‐HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation. SB 206553 has low affinity for cloned human 5‐HT2A receptors expressed in HEK 293 cells (pK1 5.8) and (pK1 <6) for a wide variety of other neurotransmitter receptors. 2 SB 206553 appears to be a surmountable antagonist of 5‐HT‐stimulated phosphoinositide hydrolysis in HEK 293 cells expressing the human 5‐HT2C receptor (pKB 9.0). 3 The compound potently (ID50 5.5 mg kg−1, p.o., 0.27 mg kg−1, i.v.) inhibited the hypolocomotor response to m‐chlorophenylpiperazine (mCPP), a putative model of 5‐HT2C/5‐HT2B receptor function in vivo. 4 At similar doses (2–20 mg kg−1, p.o.) SB 206553 increased total interaction scores in a rat social interaction test and increased punished responding in a rat Geller‐Seifter conflict test. These effects are consistent with the possession of anxiolytic properties. 5 SB 206553 also increased suppressed responding in a marmoset conflict model of anxiety at somewhat higher doses (15 and 20 mg kg−1, p.o.) but also reduced unsuppressed responding. 6 These results suggest that SB 206553 is a potent mixed 5‐HT2C/5‐HT2B receptor antagonist with selectivity over the 5‐HT2A and all other sites studied and possesses anxiolytic‐like properties. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

In vitro and in vivo profile of SB 206553, a potent 5‐HT 2C /5‐HT 2B receptor antagonist with anxiolytic‐like properties

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Publisher
Wiley
Copyright
1996 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1111/j.1476-5381.1996.tb15208.x
Publisher site
See Article on Publisher Site

Abstract

1 SB 206553 (5‐methyl‐1‐(3‐pyridylcarbamoyl)‐1,2,3,5‐tetrahydropyrrolo(2,3‐f)indole) displays a high affinity (pK1 7.9) for the cloned human 5‐HT2C receptor expressed in HEK 293 cells and the 5‐HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation. SB 206553 has low affinity for cloned human 5‐HT2A receptors expressed in HEK 293 cells (pK1 5.8) and (pK1 <6) for a wide variety of other neurotransmitter receptors. 2 SB 206553 appears to be a surmountable antagonist of 5‐HT‐stimulated phosphoinositide hydrolysis in HEK 293 cells expressing the human 5‐HT2C receptor (pKB 9.0). 3 The compound potently (ID50 5.5 mg kg−1, p.o., 0.27 mg kg−1, i.v.) inhibited the hypolocomotor response to m‐chlorophenylpiperazine (mCPP), a putative model of 5‐HT2C/5‐HT2B receptor function in vivo. 4 At similar doses (2–20 mg kg−1, p.o.) SB 206553 increased total interaction scores in a rat social interaction test and increased punished responding in a rat Geller‐Seifter conflict test. These effects are consistent with the possession of anxiolytic properties. 5 SB 206553 also increased suppressed responding in a marmoset conflict model of anxiety at somewhat higher doses (15 and 20 mg kg−1, p.o.) but also reduced unsuppressed responding. 6 These results suggest that SB 206553 is a potent mixed 5‐HT2C/5‐HT2B receptor antagonist with selectivity over the 5‐HT2A and all other sites studied and possesses anxiolytic‐like properties.

Journal

British Journal of PharmacologyWiley

Published: Feb 1, 1996

References

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