The chemorelease of norepinephrine from mouse hearts. Structure-activity relationships. I. Sympathomimetic and related amines.
The chemorelease of norepinephrine from mouse hearts. Structure-activity relationships. I. Sympathomimetic and related amines.
复制标题
小鼠心脏去甲肾上腺素的化学释放。
DOI：
10.1021/jm00321a001
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发表时间：
1966
影响因子：
7.3
通讯作者：
B. Witkop
中科院分区：
文献类型：
--
作者：
J. Daly;C. Creveling;B. Witkop
A rapid method for determining the chemorelease of cardiac norepinephrine in the mouse has been developed. Endogenous cardiac norepinephrine is prelabeled with 5/¿ curies of norepinephrine-7-3H. The cardiac norepinephrine-3!! remaining in the heart after 3 hr averages 340 m/¿ curies. Lower levels of radioactivity are found in heart when animals are injected 1 hr after the norepinephrine-3!! wuth a compound that causes chemorelease. The releas' ng potencies of a wide variety of sympathomimetic amines and related compounds have been de-termined. Structure-activity correlations are discussed.The general importance of catecholaminesand, in par-ticular, norepinephrine in the function of the cardiovascular and central nervous system has prompted investigations of drugs which effectchanges in the disposi-tion and metabolism of such amines. Many of these drugs have now become indispensible in thetreatment of hypertension and nervous disorders. Thus the tran-quilizing and hypotensive effect of reserpine has been linked to its depletion of biogenic amines in central stores1 and of norepinephrine in sympathetically innervated tissues ofthe cardiovascular system. 2 Simi-larly, the hypotensive-methyl aromatic amino acids, such as-methyldopa, originally synthesized as inhibitors of aromatic amino acid decarboxylase, have been shown to owe their hypotensive action to a long-lasting depletion of norepinephrine stores by release of the en-dogenous amine rather than by inhibition of its syn-thesis. 3 Other hypotensive agents, such as guanethi-dine, 4 bretylium, 6 and the monoamine oxidase inhib-itors, 6 also effect the storage and/or release of nor-epinephrine.
