[en] Antipsychotic therapy is frequently associated with several side effects such as hyperprolactinemia. The influence of a putative antipsychotic JL 13 on prolactin release was assessed after intraperitoneal injection in gentled male rats in comparison with clozapine and haloperidol. A total of 30 or 150 min after administration, whole blood was collected for preparing serum samples. Prolactin was quantified by radioimmunoassay method. At 30 min, JL 13 like clozapine, increased prolactin concentration only at the higher dose (30 mg/kg) while haloperidol at both tested doses induced a dramatic increase of prolactin concentration. At 150 min after injection, only haloperidol (0.3 mg/kg) significantly increased serum prolactin level. This minimal effect on prolactinemia reinforces the similarity of clozapine and JL 13 regarding the atypical antipsychotic profile. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
Disciplines :
Neurosciences & behavior
Author, co-author :
Liégeois, Jean-François ; Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Bruhwyler, J.
Hendrick, J. C.
Delarge, J.
Legros, Jean-Jacques ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Damas, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Minimal effects of JL 13, a pyridobenzoxazepine derivative with an antipsychotic potential, on circulating prolactin levels in male rats
Bhana N., Foster R.H., Olney R., Plosker G.L. (2001) Olanzapine. An updated review of its use in the management of schizophrenia. Drugs 61:111-161.
Bowden C.R., Voina S.J., Woestenborghs R., De Coster R., Heykants J. (1992) Stimulation by risperidone of rat prolactin secretion in vivo and in cultured pituitary cells in vitro. J. Pharmacol. Exp. Ther. 262:699-706.
Bruhwyler J., Liégeois J.-F., Bergman J., Carey G., Goudie A., Taylor A., Meltzer H.Y., Delarge J., Géczy J. (1997) JL13, a pyridobenzoxazepine compound with potential atypical antipsychotic activity: A review of its behavioural properties. Pharmacol. Res. 36:255-264.
Casey D.E., Bruhwyler J., Delarge J., Géczy J., Liégeois J.-F. (2001) The behavioral effects of acute and chronic JL 13, a putative antipsychotic, in Cebus non-human primates. Psychopharmacology 157:228-235.
Ellenbroek B.A., Liégeois J.-F., Bruhwyler J., Cools A.R. (2001) The effects of JL 13, a pyridobenzoxazepine with potential atypical antipsychotic activity, in animal models for schizophrenia. J. Pharmacol. Exp. Ther. 298:386-391.
Fessler R.G., Deyo S.N., Meltzer H.Y., Miller R.J. (1984) Evidence that the medial and dorsal raphe nuclei mediate serotonergically-induced increases in prolactin release from the pituitary. Brain Res. 299:231-237.
Gudelsky G.A., Koenig J.I., Simonovic M., Koyama T., Ohmori T., Meltzer H.Y. (1987) Differential effects of haloperidol, clozapine, and fluperlapine on tuberoinfundibular dopamine neurons and prolactin secretion in the rat. J. Neural. Transm. 68:227-240.
Guiso G., Caccia S. (2001) Distribution of the methylpiperazinopyridobenzoxazepine derivative JL 13, a potential antipsychotic, in rat brain. J. Pharm. Pharmacol. 53:317-321.
Huang M.L., Van Peer A., Woestenborghs R. (1993) Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin. Pharmacol. Ther. 54:257-268.
Kane J., Honigfeld G., Singer J., Meltzer H.Y. (1988) Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch. Gen. Psychiatry 45:789-796.
Kapur S., Roy P., Daskalakis J., Remington G., Zipursky R. (2001) Increased dopamine D2 receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Am. J. Psychiatry 158:311-314.
Liégeois J.-F., Rogister F., Bruhwyler J., Damas J., Nguyen T.P., Inarejos M.O., Chleide E., Mercier M., Delarge J. (1994) Pyridobenzoxazepine and pyridobenzothiazepine derivatives as potential central nervous system agents: Synthesis and neurochemical study. J. Med. Chem. 37:519-525.
Meltzer H.Y., Daniels S., Fang V.S. (1976) Clozapine increases rat serum prolactin levels. Life Sci. 17:339-342.
Meltzer H.Y., Goode D.J., Schyve P.M., Young M., Fang V.S. (1979) Effect of clozapine on human serum prolactin levels. Am. J. Psychiatry 136:1550-1555.
Meltzer H.Y., Matsubara S., Lee J.-C. (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J. Pharmacol. Exp. Ther. 251:238-246.
Petty R.G. (1999) Prolactin and antipsychotic medications: Mechanism of action. Schizophr. Res. 35.
Saller C.F., Czupryna M.J., Salama A.I. (1990) 5-HT2 receptor blockade by ICI 169,369 and other 5-HT2 antagonists modulates the effects of D-2 dopamine receptor blockade. J. Pharmacol. Exp. Ther. 253:1162-1170.
Saller C.F., Salama A.I. (1993) Seroquel: Biochemical profile of a potential atypical antipsychotic. Psychopharmacology 112:285-292.
Seutin V., Liégeois J.-F., Massotte L., Géczy J., Dresse A. (2000) Blockade of the inhibitory effect of BHT920, a D2 agonist, on substantia nigra and VTA dopaminergic neurons by JL 13, clozapine, and haloperidol. Int. J. Neuropsychopharmacol. 3.