EFFECTS OF NOVEL CATECHOL ETHER IMIDAZOLIDINONES ON CALCIUM-INDEPENDENT PHOSPHODIESTERASE ACTIVITY, [H-3] ROLIPRAM BINDING, AND RESERPINE-INDUCED HYPOTHERMIA IN MICE

被引:15
作者
KOE, BK
LEBEL, LA
NIELSEN, JA
RUSSO, LL
SACCOMANO, NA
VINICK, FJ
WILLIAMS, IH
机构
[1] Central Research Division, Pfizer Inc., Groton, Connecticut
关键词
calcium‐independent phosphodiesterase; catecholethr; imidazolidinones; reserpine‐induced hypothernmia; [!sup]3[!/sup]H]rolipram binding;
D O I
10.1002/ddr.430210206
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of new catechol ether imidazolidinones incorporating structural features of rolipram and Ro 20‐1724 were synthesized as inhibitors of the calcium‐independent phosphodiesterase (IPDE) from rat cerebral cortex. Several compounds were found to be more potent than rolipram as IPDE inhibitors; all of the compounds studied were more potent than Ro 20‐1724. The new imidazolidinones also showed affinity for the [3H]rolipram binding site in mouse brain membranes and reversed reserpine‐induced hypothermia in mice at relatively low doses. In vitro, the potency of these compounds as IPDE inhibitors did not correlate with their affinity for the [3H]rolipram binding site. Reversal of reserpine hypothermia by the imidazolidinones (“antidepressant effect”) could not be linked definitively to either in vitro activity. Copyright © 1990 Wiley‐Liss, Inc.
引用
收藏
页码:135 / 142
页数:8
相关论文
共 21 条
[1]  
ASKEW BM, 1963, LIFE SCI, V4, P725
[3]  
ECKMANN F, 1988, CURR THER RES CLIN E, V43, P291
[4]   ROLIPRAM IN MAJOR DEPRESSIVE DISORDER - RESULTS OF A DOUBLE-BLIND COMPARATIVE-STUDY WITH IMIPRAMINE [J].
HEBENSTREIT, GF ;
FELLERER, K ;
FICHTE, K ;
FISCHER, G ;
GEYER, N ;
MEYA, U ;
SASTREYHERNANDEZ, M ;
SCHONY, W ;
SCHRATZER, M ;
SOUKOP, W ;
TRAMPITSCH, E ;
VAROSANEC, S ;
ZAWADA, E ;
ZOCHLING, R .
PHARMACOPSYCHIATRY, 1989, 22 (04) :156-160
[5]  
HOROWSKI R, 1985, CURR THER RES CLIN E, V38, P23
[6]   EFFECTS OF ROLIPRAM, A NOVEL ANTIDEPRESSANT, ON MONOAMINE METABOLISM IN RAT-BRAIN [J].
KEHR, W ;
DEBUS, G ;
NEUMEISTER, R .
JOURNAL OF NEURAL TRANSMISSION, 1985, 63 (01) :1-12
[7]  
KOE BK, 1983, J PHARMACOL EXP THER, V226, P686
[8]   THE EFFECT OF A SELECTIVE PHOSPHODIESTERASE INHIBITOR, ROLIPRAM, ON MURICIDE IN OLFACTORY BULBECTOMIZED RATS [J].
MIZOKAWA, T ;
KIMURA, K ;
IKOMA, Y ;
HARA, K ;
OSHINO, N ;
YAMAMOTO, T ;
UEKI, S .
JAPANESE JOURNAL OF PHARMACOLOGY, 1988, 48 (03) :357-364
[9]   EFFECT OF LONG-TERM ROLIPRAM ADMINISTRATION ON THE SENSITIVITY OF ALPHA-2-ADRENOCEPTORS IN RAT-BRAIN [J].
MUSTAFA, MR ;
STOLZ, JF ;
LUSCOMBE, DK .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 148 (02) :171-177
[10]   SELECTIVE-INHIBITION OF ONE OF THE CYCLIC-AMP PHOSPHODIESTERASES FROM RAT-BRAIN BY THE NEUROTROPIC COMPOUND ROLIPRAM [J].
NEMOZ, G ;
PRIGENT, AF ;
MOUEQQIT, M ;
FOUGIER, S ;
MACOVSCHI, O ;
PACHECO, H .
BIOCHEMICAL PHARMACOLOGY, 1985, 34 (16) :2997-3000