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LONG‐TERM EFFECTS OF N ‐2‐CHLOROETHYL‐ N ‐ETHYL‐2‐BROMOBENZYLAMINE HYDROCHLORIDE ON NORADRENERGIC NEURONES IN THE RAT BRAIN AND HEART
Author(s) -
ROSS S.B.
Publication year - 1976
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1976.tb08619.x
Subject(s) - norepinephrine , hydrochloride , term (time) , medicine , chemistry , endocrinology , anesthesia , physics , dopamine , organic chemistry , quantum mechanics
1 N ‐2‐Chloroethyl‐ N ‐ethyl‐2‐bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long‐term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatum (dopamine neurones) and on the uptake of 5‐hydroxytryptamine (5‐HT) in various brain regions. 2 In vitro DSP 4 inhibited the noradrenaline uptake in a cortical homogenate with an IC 50 value of 2 μ m but was more than ten times less active on the dopamine uptake in a striatal homogenate and the 5‐HT uptake in a cortical homogenate. 3 DSP 4 (50 mg/kg i.p.) inhibited the uptake of noradrenaline in the rat heart atrium in vitro but this action was terminated within 2 weeks. 4 DSP 4 (50 mg/kg i.p.) caused a decrease in the dopamine‐β‐hydroxylase (DBH) activity in the rat brain and heart. The onset of this effect was slow; in heart a lag period of 2–4 days was noted. In brain the DBH‐activity in cerebral cortex was much more decreased than that in hypothalamus which was only slightly affected. A significant effect was still found 8 months after the injection. The noradrenaline concentration in the brain was greatly decreased for at least two weeks, whereas noradrenaline in heart was only temporarily reduced. 5 The long‐term effects of DSP 4 on the noradrenaline accumulation, the DBH activity and noradrenaline concentration in the rat brain were antagonized by desipramine (10 mg/kg i.p.). 6 It is suggested that DSP 4 primarily attacks the membranal noradrenaline uptake sites forming a covalent bond and that the nerve terminals, as a result of this binding, degenerate.