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Acute drug‐induced inactivation of the h5‐HT7 receptor: a pharmacological profile
Author(s) -
Knight Jessica,
Smith Carol,
Toohey Nicole,
Teitler Milt
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.724.12
Subject(s) - ritanserin , pharmacology , metergoline , chemistry , amisulpride , antipsychotic , risperidone , receptor antagonist , receptor , typical antipsychotic , atypical antipsychotic , antagonist , 5 ht receptor , psychology , medicine , serotonin , biochemistry , schizophrenia (object oriented programming) , psychiatry
The h5‐HT 7 R is one of 13 5‐HT receptors expressed in humans. It is involved in the control of cognition, emotion, and cardiovascular tone. Recently we reported that a 30 min exposure to nM levels of the antipsychotic drug risperidone results in an inactivation of the h5‐HT 7 R‐mediated stimulation of cAMP production (Smith et al, Mol. Pharmacol., 2006). To further investigate this unusual effect of this highly prescribed drug we have been testing other drugs for similar inactivating properties. 9‐OH‐risperidone, the active metabolite of risperidone, and methiothepin, a potent 5‐HT receptor antagonist, also potently inactivate the receptor. Preliminary studies indicate amoxapine, ritanserin, metergoline, lisuride, bromocryptine, SB‐269970 also produce this effect: clozapine, TFMPP and tenilapine did not produce the inactivating effects. It appears that a majority of h5‐HT 7 receptor antagonists produce this unusual and dramatic effect. h5‐HT 7 ‐mediated MAPK phosphorylation is also inactivated by risperidone, 9‐OH‐risperidone, and methiothepin, consistent with data indicating an irreversible or pseudo‐irreversible interaction is occurring between the drugs and the receptor. Further studies are underway to investigate the mechanism and in vivo relevance of these observations. Supported by MH56650 (M.T.)