Molecular features of the prazosin molecule required for activation of Transport-P

被引：72

作者：

Mendes da Silva, Joaquim Fernando ^{[1
,2
]}

Walters, Marcus ^{[1
]}

Al-Damluji, Saad ^{[3
,4
]}

Ganellin, C. Robin ^{[1
]}

机构：

[1] UCL, Dept Chem, Christopher Ingold Labs, London WC1H 0AJ, England

[2] Univ Fed Rio de Janeiro, Dept Organ Chem, BR-21941 Rio De Janeiro, Brazil

[3] Royal Free & Univ Coll Med Sch, Div Endocrinol, London NW3 2PF, England

[4] Royal Free & Univ Coll Med Sch, Div Biochem, London NW3 2PF, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 15期

关键词：

Transport-P; prazosin; peptidergic neurones; quinazoline; furan; antidepressant; amine uptake;

D O I：

10.1016/j.bmc.2008.06.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Closely related structural analogues of prazosin have been synthesised and tested for inhibition and activation of Transport-P in order to identify the structural features of the prazosin molecule that appear to be necessary for activation of Transport-P. So far, all the compounds tested are less active than prazosin. It is shown that the structure of prazosin appears to be very specific for the activation. Only quinazolines have been found to activate, and the presence of the 6,7-dimethoxy and 4-amino groups appears to be critically important. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7254 / 7263

页数：10

共 22 条

[1] Release of amines from acidified stores following accumulation by Transport-P [J].

Al-Damluji, S ;

Shen, WB .

BRITISH JOURNAL OF PHARMACOLOGY, 2001, 132 (04) :851-860

[2] Structural properties of phenylethylamine derivatives which inhibit transport-P in peptidergic neurones [J].

Al-Damluji, S ;

Kopin, IJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1998, 124 (04) :693-702

[3] α1B adrenergic receptors in gonadotrophin-releasing hormone neurones:: relation to Transport-P [J].

Al-Damluji, S ;

Shen, WB ;

White, S ;

Barnard, EA .

BRITISH JOURNAL OF PHARMACOLOGY, 2001, 132 (01) :336-344

[4] The Mechanism of Action of Antidepressants: A Unitary Hypothesis Based on Transport-P [J].

Al-Damluji, Saad .

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, 2004, 3 (03) :201-216

[5] Visual detection of transport-P in peptidergic neurones [J].

AlDamluji, S ;

Porter, D ;

Krsmanovic, LZ ;

Knutson, JR ;

Kopin, IJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1997, 120 (05) :876-882

[6] HIGH-AFFINITY UPTAKE OF NORADRENALINE IN POSTSYNAPTIC NEURONS [J].

ALDAMLUJI, S ;

KRSMANOVIC, LZ ;

CATT, KJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1993, 109 (02) :299-307

[7] Functional properties of the uptake of amines in immortalised peptidergic neurones (transport-P) [J].

AlDamluji, S ;

Kopin, IJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (01) :111-118

[8] Binding and competitive inhibition of amine uptake at postsynaptic neurones (transport-P) by tricyclic antidepressants [J].

AlDamluji, S ;

Kopin, IJ .

BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (05) :811-816

[9]

ALDAMLUJI S, 2002, BR J PHARM, V136

[10] SYNTHESIS AND IDENTIFICATION OF MAJOR METABOLITES OF PRAZOSIN FORMED IN DOG AND RAT [J].

ALTHUIS, TH ;

HESS, HJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (01) :146-149

← 1 2 3 →