当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > ADN-1184 a monoaminergic ligand with 5-HT(6/7) receptor antagonist activity: pharmacological profile and potential therapeutic utility.

ADN-1184 a monoaminergic ligand with 5-HT(6/7) receptor antagonist activity: pharmacological profile and potential therapeutic utility.

Abstract：

BACKGROUND AND PURPOSE:Many dementia patients exhibit behavioural and psychological symptoms (BPSD) that include psychosis, aggressivity, depression and anxiety. Antipsychotic drugs are frequently prescribed but fail to significantly attenuate mood deficits, may interfere with cognitive function and are associated with motor and cardiac side effects, which are problematic in elderly patients. A need therefore exists for drugs that are better suited for the treatment of BPSD. EXPERIMENTAL APPROACH:We used in vitro cellular and in vivo behavioural tests to characterize ADN-1184, a novel arylsulfonamide ligand with potential utility for treatment of BPSD. KEY RESULTS:ADN-1184 exhibits substantial 5-HT6 /5-HT7 /5-HT2A /D2 receptor affinity and antagonist properties in vitro. In tests of antipsychotic-like activity, it reversed MK-801-induced hyperactivity and stereotypies and inhibited conditioned avoidance response (MED = 3 mg·kg(-1) i.p.). Remarkably, ADN-1184 also reduced immobility time in the forced swim test at low doses (0.3 and 1 mg·kg(-1) i.p.; higher doses were not significantly active). Notably, up to 30 mg·kg(-1) ADN-1184 did not impair memory performance in the passive avoidance test or elicit significant catalepsy and only modestly inhibited spontaneous locomotor activity (MED = 30 mg·kg(-1) i.p.). CONCLUSIONS AND IMPLICATIONS:ADN-1184 combines antipsychotic-like with antidepressant-like properties without interfering with memory function or locomotion. This profile is better than that of commonly used atypical antipsychotics tested under the same conditions and suggests that it is feasible to identify drugs that improve BPSD, without exacerbating cognitive deficit or movement impairment, which are of particular concern in patients with dementia.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Kołaczkowski M,Mierzejewski P,Bieńkowski P,Wesołowska A,Newman-Tancredi A

doi

10.1111/bph.12509

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

973-84

issue

eissn

0007-1188

issn

1476-5381

journal_volume

171

pub_type

杂志文章

在线工具

ADN-1184 a monoaminergic ligand with 5-HT(6/7) receptor antagonist activity: pharmacological profile and potential therapeutic utility.