Linked Life Data

7824038

Source:http://linkedlifedata.com/resource/pubmed/id/7824038

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-2-14
pubmed:abstractText
N-(diethylamino-ethyl)-4-chloro-5-cyano-2-methoxy-benzamide-hydrochlo rid e (CGP 25454A) is a new benzamide derivative now in clinical trials in patients with major depression. Here we describe some basic neurochemical and behavioural properties in animal experiments. In vitro, CGP 25454A increased the field-stimulated [3H]- and [14C]-overflow from rat striatal slices preloaded with [3H]dopamine and [14C]choline, indicating that CGP 25454A was able to enhance the release of both dopamine (DA) and acetylcholine (ACh). However, CGP 25454A was 12.9 times more potent in increasing, by 1/6 of the apparent maximal increase, the release of [3H]DA than that of [14C]ACh. In vivo, CGP 25454A increased [3H]spiperone binding to receptors of the D2 family in rat striatum by 90-110% (ED50: 13 mg/kg i.p.). As a similar increase in [3H]spiperone binding was found with a variety of agents which increase the synaptic concentration of endogenous DA, the effect of CGP 25454A most probably reflects an enhanced release of DA under in vivo conditions. At 30-100 mg/kg, CGP 25454A inhibited [3H]spiperone binding in the pituitary of the same animals as a result of a blockade of postsynaptic DA receptors. This dual mode of action was also apparent in terms of behavioral changes. At doses as low as 5-10 mg/kg, CGP 25454A produced a weak stimulation, suggested by a trend of increased spontaneous rearing and corroborated by a significant potentiation of the elevated rearing induced by (+)-amphetamine. By contrast, at doses of 30-100 mg/kg, it exerted clear-cut sedative and neuroleptic-like properties.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
350
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-8
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
CGP 25454A, a novel and selective presynaptic dopamine autoreceptor antagonist.
pubmed:affiliation
Research Department, Chiba, Basel, Switzerland.
pubmed:publicationType
Journal Article