Cyclic AMP Response to Norepinephrine
Metabolites of Chlorpromazine
Springer Online Journal Archives 1860-2000
Abstract Tissue slices were prepared from paired areas of the rat hypothalamus and brain stem. Exposure of the brain slices for 6 min to 5×10−5 M norepinephrine (NE) consistently resulted in a 3- to 5-fold increase in the level of adenosine 3′,5′monophosphate (cyclic AMP). Prochlorperazine and 7-hydroxychlorpromazine at 10−5 M antagonized the increase of the cyclic nucleotide elicited by NE in the hypothalamus and the brain stem (p〈0.01), while 8-hydroxychlorpromazine and imipramine were effective in only the hypothalamus. The remaining metabolites of chlorpromazine (CPZ), 7-methoxy-CPZ, 3,7-dihydroxy-CPZ, 7-hydroxy-8-methoxy-CPZ, 8-hydroxy-7-methoxy-CPZ, and 7,8-dihydroxypromazine failed to modify the NE-induced cyclic AMP response at 10−5 M. d-Amphetamine and p-chloroamphetamine at a concentration of 10−5 M did not affect the levels of cyclic AMP either in the precence or absence of NE. High concentrations of lithium antagonized the cyclic AMP response to NE in the hypothalamus. None of the drugs altered the basal levels of the cyclic nucleotide in vitro; p-chloroamphetamine, however, markedly reduced the basal level of cyclic AMP after the intraperitoneal injection of the drug.
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