Disease relevance of az-Dsp 4

• Behavioral and neurochemical effects of noradrenergic depletions with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine in 6-hydroxydopamine-induced rat model of Parkinson's disease [1].

Psychiatry related information on az-Dsp 4

• Rats treated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenergic neurotoxin, showed no differences compared to control rats in the number of head dips, a measure of exploratory behavior [2].
• We found that microinjection of the specific noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, into these regions had no effect on the increase in paradoxical sleep duration seen after SD, suggesting that noradrenergic (NA) innervation of the prefrontal cortex and DG are not involved in sleep rebound regulation [3].
• We previously showed that the noradrenergic locus coeruleus (NA-LC) was involved in the regulatory mechanisms of the paradoxical sleep rebound following a 10 h sleep deprivation by using a systemic injection of a specific neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) [4].

High impact information on az-Dsp 4

• The association of [3H]desipramine binding sites with neuronal norepinephrine uptake sites is supported further by the selective abolition of high affinity [3H]desipramine binding following the destruction of central norepinephrine neurons by intraperitoneal administration of DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) [5].
• Similarly, the association of [3H]mazindol binding sites with neuronal norepinephrine uptake sites in cerebral cortex is supported by the reduction of [3H]mazindol binding to cortical membranes following destruction of noradrenergic neurons by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine [6].
• DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a selective noradrenaline (NA) uptake blocker, is capable of inducing long-lasting depletion of NA in some noradrenergic axon terminals and of subsequently causing cell death to NA neuronal cell bodies in rodents [7].
• In this study exploratory and amphetamine-induced behavior in rats with persistently high or low exploratory activity (HE and LE, respectively) was examined before and after a partial denervation of the locus coeruleus (LC) projections with the selective neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 10 mg/kg) [8].
• Effects of low dose N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine administration on exploratory and amphetamine-induced behavior and dopamine D2 receptor function in rats with high or low exploratory activity [8].

Chemical compound and disease context of az-Dsp 4

• Noradrenergic lesion with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) decreases dopamine release in the striatum and enhances catalepsy in experimental models of Parkinson's disease [9].

Anatomical context of az-Dsp 4

• We have previously analyzed the response of locus coeruleus (LC) neurons to systemic administration of the noradrenergic (NE) neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to adult rats [10].
• Rats were pretreated with the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (40 mg/kg, i.p.), which after three days had reduced noradrenaline levels in the medial prefrontal cortex by 84% [11].
• The response of c-fos to photo-stimulation was also significantly lower in the visual cortex of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-treated young rats [12].
• Effects of the catecholaminergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on adrenal chromaffin cells in culture [13].
• N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a neurotoxin with high selectivity for noradrenergic terminals, was administered into kitten cerebral ventricles [14].

Associations of az-Dsp 4 with other chemical compounds

• To study the role of the noradrenergic system in the chronic regulation of neurotrophin messenger RNA expression, chemical [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, 6-hydroxydopamine] and mechanical (knife-cut axotomy) lesions were performed, in the rat, and neurotrophin messenger RNAs analysed after 14 and 35 days [15].
• The present studies have examined the effects of two types of noradrenergic denervation [neurotoxic: via N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) treatment; and pharmacologic: via chronic beta adrenergic receptor blockade] on the 5-HT2-mediated head shake response and cortical beta adrenergic and 5-HT2 receptor number in the rat [16].
• In vivo treatment with 6-OHDA or N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) also potentiated the electrophysiological response to NE in a manner similar to that observed with acute in vitro 6-OHDA pretreatment [17].
• The improvement of recovery evoked by TRH (3 mg/kg i.v.) after concussion was not affected by i.p. pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, alpha-methyl-para-tyrosine, p-chlorophenylalanine, scopolamine or methylscopolamine [18].
• In the present study, we found that the difference in clonidine-induced analgesia between these two strains was abolished after lesioning the presynaptic noradrenergic neurons with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) [19].

Gene context of az-Dsp 4

• Impaired recovery of noradrenaline levels in apolipoprotein E-deficient mice after N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine lesion [20].
• In contrast, no significant change in zif268 expression was detected between normal and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-treated animals [12].
• Tumor necrosis factor-alpha was infused into the basal forebrain of young mice pretreated with a norepinephrine neuronal toxin, N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine (DSP4), with the expectation that the loss of noradrenergic input would enhance the loss of cholinergic neurons [21].
• We tested the hypothesis that Long-Evans (LE) and Sprague-Dawley (SD) rat strains were equally sensitive to the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) with respect to central lesions of locus coeruleus (LC) terminals as measured by immunohistochemical localization of dopamine-beta-hydroxylase (D beta H) [22].

Analytical, diagnostic and therapeutic context of az-Dsp 4

• The degeneration of central noradrenergic terminals induced by an intraperitoneal injection of the toxin N-(2-chloroethyl)-N-ethyl-2- bromobenzylamine in rats decreased by 80% the maximal number of cerebellar TY binding sites, while not affecting striatal binding [23].
• DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], another potent substance used for sympathetic denervation, had a suppressive effect similar to that of 6-OHDA [24].

References