Abstract
Many antipsychotics have marked antagonist effects at 5-hydroxytryptamine (5-HT(2C)) receptors in vitro, which, however, have been difficult to show in behavioral assays. Here, we used two assays - hypolocomotion and hypophagia induced by the 5-HT(2C) receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) - to try to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics in vivo. Clozapine, olanzapine, pipamperone, and trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz-[2,3:6,7]oxepino[4,5-C] pyrrolidino maleate (ORG 5222), modestly, but significantly, attenuated mCPP (10 mg/kg)-induced hypolocomotion. In contrast, risperidone and loxapine were inactive. The putative antipsychotic ORG 5222 significantly attenuated mCPP (5 mg/kg)-induced hypophagia, whereas the other antipsychotics were inactive. Selective antagonists at dopamine D2-like receptors, α1-adrenoceptors, α2-adrenoceptors, or muscarinic receptors were not able to antagonize the effects of mCPP in either assay. The results suggest that mCPP-induced hypolocomotion can be used to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics, whereas mCPP-induced hypophagia appeared to be sensitive only to compounds highly selective for 5-HT(2C) receptors. Together, these assays may help to characterize functional, in vivo, 5-HT(2C) receptor antagonist properties of antipsychotics. Copyright (C) 2000 Elsevier Science B.V.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 57-67 |
| Number of pages | 11 |
| Journal | European Journal of Pharmacology |
| Volume | 388 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 24 2000 |
| Externally published | Yes |
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Keywords
- 5-HT (5-hydroxytryptamine)
- 5-HT(2C) receptor
- Antipsychotic
- Behavior
- Food intake
- Hypolocomotion
- Hypophagia
- Locomotor activity
- mCPP-(3-chlorophenyl)piperazine
- Neuroleptic
- serotonin
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds. / Prinssen, Eric P M; Koek, Wouter; Kleven, Mark S.
In: European Journal of Pharmacology, Vol. 388, No. 1, 24.01.2000, p. 57-67.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds
AU - Prinssen, Eric P M
AU - Koek, Wouter
AU - Kleven, Mark S.
PY - 2000/1/24
Y1 - 2000/1/24
N2 - Many antipsychotics have marked antagonist effects at 5-hydroxytryptamine (5-HT(2C)) receptors in vitro, which, however, have been difficult to show in behavioral assays. Here, we used two assays - hypolocomotion and hypophagia induced by the 5-HT(2C) receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) - to try to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics in vivo. Clozapine, olanzapine, pipamperone, and trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz-[2,3:6,7]oxepino[4,5-C] pyrrolidino maleate (ORG 5222), modestly, but significantly, attenuated mCPP (10 mg/kg)-induced hypolocomotion. In contrast, risperidone and loxapine were inactive. The putative antipsychotic ORG 5222 significantly attenuated mCPP (5 mg/kg)-induced hypophagia, whereas the other antipsychotics were inactive. Selective antagonists at dopamine D2-like receptors, α1-adrenoceptors, α2-adrenoceptors, or muscarinic receptors were not able to antagonize the effects of mCPP in either assay. The results suggest that mCPP-induced hypolocomotion can be used to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics, whereas mCPP-induced hypophagia appeared to be sensitive only to compounds highly selective for 5-HT(2C) receptors. Together, these assays may help to characterize functional, in vivo, 5-HT(2C) receptor antagonist properties of antipsychotics. Copyright (C) 2000 Elsevier Science B.V.
AB - Many antipsychotics have marked antagonist effects at 5-hydroxytryptamine (5-HT(2C)) receptors in vitro, which, however, have been difficult to show in behavioral assays. Here, we used two assays - hypolocomotion and hypophagia induced by the 5-HT(2C) receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) - to try to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics in vivo. Clozapine, olanzapine, pipamperone, and trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz-[2,3:6,7]oxepino[4,5-C] pyrrolidino maleate (ORG 5222), modestly, but significantly, attenuated mCPP (10 mg/kg)-induced hypolocomotion. In contrast, risperidone and loxapine were inactive. The putative antipsychotic ORG 5222 significantly attenuated mCPP (5 mg/kg)-induced hypophagia, whereas the other antipsychotics were inactive. Selective antagonists at dopamine D2-like receptors, α1-adrenoceptors, α2-adrenoceptors, or muscarinic receptors were not able to antagonize the effects of mCPP in either assay. The results suggest that mCPP-induced hypolocomotion can be used to characterize the 5-HT(2C) receptor antagonist properties of antipsychotics, whereas mCPP-induced hypophagia appeared to be sensitive only to compounds highly selective for 5-HT(2C) receptors. Together, these assays may help to characterize functional, in vivo, 5-HT(2C) receptor antagonist properties of antipsychotics. Copyright (C) 2000 Elsevier Science B.V.
KW - 5-HT (5-hydroxytryptamine)
KW - 5-HT(2C) receptor
KW - Antipsychotic
KW - Behavior
KW - Food intake
KW - Hypolocomotion
KW - Hypophagia
KW - Locomotor activity
KW - mCPP-(3-chlorophenyl)piperazine
KW - Neuroleptic
KW - serotonin
UR - http://www.scopus.com/inward/record.url?scp=0033984692&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033984692&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00859-6
DO - 10.1016/S0014-2999(99)00859-6
M3 - Article
C2 - 10657547
AN - SCOPUS:0033984692
VL - 388
SP - 57
EP - 67
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -