In vivo properties of SB 200646A, a 5‐HT 2C/2B receptor antagonist

In vivo properties of SB 200646A, a 5‐HT 2C/2B receptor antagonist 1 SB 200646A, N‐(1‐methyl‐5‐indolyl)‐N′‐(3‐pyridyl) urea hydrochloride, the first reported selective 5‐HT2C/2B over 5‐HT2A receptor antagonist, (pK1 rat 5‐HT2C receptor 6.9, pA2 rat 5‐HT2B receptor 7.5, pKi rat 5‐HT2A receptor 5.2) dose‐dependently blocked a putative rat model of 5‐HT2C receptor activation; 1‐(3‐chlorophenyl)piperazine (mCPP, 5 mg kg−1, i.p. 20 min pretest)‐induced hypolocomotion (estimated ID50 19.2 mg kg−1, p.o.). 2 SB 200646A also blocked another putative in vivo model of 5‐HT2C receptor function; mCPP (5 mg kg−1, i.p. 20 min pretest)‐induced hypophagia in 23 h food‐deprived rats (estimated ID50 18.3 mg kg−1, p.o.). 3 SB 200646A did not antagonize 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI)‐induced head shakes in rats at doses up to 200 mg kg−1, p.o., an effect thought to be mediated by 5‐HT2A receptors for which SB 200646A has its next highest affinity (50 fold less) after the 5‐HT2C and 5‐HT2B sites. 4 SB 200646A (20, 40 mg kg−1, p.o., 1 h pretest) also reversed mCPP (0.5 mg kg−1, i.p., 30 min pretest)‐induced anxiety in the social interaction test, under low light familiar conditions. 5 When given alone, under high light unfamiliar conditions, SB 200646A (2–40 mg kg−1, p.o.) increased active social interaction without affecting locomotor activity in the rat social interaction test. This is consistent with an anxiolytic action of SB 200646A. 6 These results indicate that SB 200646A has in vivo efficacy and that 5‐HT2C or 5‐HT2B receptors are indeed likely to mediate mCPP‐induced hypolocomotion, hypophagia and anxiogenesis. They also suggest that 5‐HT2C/2B receptor blockade induces anxiolysis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

In vivo properties of SB 200646A, a 5‐HT 2C/2B receptor antagonist

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Publisher
Wiley
Copyright
1994 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1111/j.1476-5381.1994.tb14808.x
Publisher site
See Article on Publisher Site

Abstract

1 SB 200646A, N‐(1‐methyl‐5‐indolyl)‐N′‐(3‐pyridyl) urea hydrochloride, the first reported selective 5‐HT2C/2B over 5‐HT2A receptor antagonist, (pK1 rat 5‐HT2C receptor 6.9, pA2 rat 5‐HT2B receptor 7.5, pKi rat 5‐HT2A receptor 5.2) dose‐dependently blocked a putative rat model of 5‐HT2C receptor activation; 1‐(3‐chlorophenyl)piperazine (mCPP, 5 mg kg−1, i.p. 20 min pretest)‐induced hypolocomotion (estimated ID50 19.2 mg kg−1, p.o.). 2 SB 200646A also blocked another putative in vivo model of 5‐HT2C receptor function; mCPP (5 mg kg−1, i.p. 20 min pretest)‐induced hypophagia in 23 h food‐deprived rats (estimated ID50 18.3 mg kg−1, p.o.). 3 SB 200646A did not antagonize 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI)‐induced head shakes in rats at doses up to 200 mg kg−1, p.o., an effect thought to be mediated by 5‐HT2A receptors for which SB 200646A has its next highest affinity (50 fold less) after the 5‐HT2C and 5‐HT2B sites. 4 SB 200646A (20, 40 mg kg−1, p.o., 1 h pretest) also reversed mCPP (0.5 mg kg−1, i.p., 30 min pretest)‐induced anxiety in the social interaction test, under low light familiar conditions. 5 When given alone, under high light unfamiliar conditions, SB 200646A (2–40 mg kg−1, p.o.) increased active social interaction without affecting locomotor activity in the rat social interaction test. This is consistent with an anxiolytic action of SB 200646A. 6 These results indicate that SB 200646A has in vivo efficacy and that 5‐HT2C or 5‐HT2B receptors are indeed likely to mediate mCPP‐induced hypolocomotion, hypophagia and anxiogenesis. They also suggest that 5‐HT2C/2B receptor blockade induces anxiolysis.

Journal

British Journal of PharmacologyWiley

Published: Mar 1, 1994

References

  • Hippocampal noradrenaline and serotonin release over 24 hours as measured by the dialysis technique in freely moving rats: correlation to behavioural activity state, effect of handling and tail pinch
    KALEN, KALEN; ROSENGREN, ROSENGREN; LINDVALL, LINDVALL; BJORKLUND, BJORKLUND
  • Evidence that mCPP may have behavioural effects mediated by 5‐HT 1C receptors
    KENNETT, KENNETT; CURZON, CURZON
  • Potencies of antagonists indicate that 5‐HT 1C receptors mediate 1–3(chlorophenyl) piperazine‐induced hypophagia
    KENNETT, KENNETT; CURZON, CURZON
  • Mianserin and doxepin in the treatment of outpatient depression with anxiety
    KHAN, KHAN; BENNIE, BENNIE; STULEMEIJER, STULEMEIJER; RAVENS, RAVENS
  • Mianserin in the treatment of depressive illness and anxiety states in general practice
    MURPHY, MURPHY
  • Comparative double‐blind trial of mianserin hydrochloride (Organon GB94) and diazepam in patients with depressive illness
    RUSSELL, RUSSELL; NIAZ, NIAZ; WAKELING, WAKELING; SLADE, SLADE
  • Anxiogenic‐like effect of infusing 1‐(3‐chlorophenyl) piperazine (mCPP) into the hippocampus
    WHITTON, WHITTON; CURZON, CURZON
  • Effect of established and putative anxiolytics on extracellular 5‐HT and 5‐HIAA in the ventral hippocampus of rats during behaviour on the elevated X‐maze
    WRIGHT, WRIGHT; UPTON, UPTON; MARSDEN, MARSDEN

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