British Journal of Pharmacology and ChemotherapyVolume 33, Issue 2 p. 257-265 Free Access ASPECTS OF THE BIOGENIC AMINE-DEPLETING ACTIVITY OF ETHYL 3-ACETAMIDO-4H-PYRROLO-[3,4-c]ISOXAZOLE-5(6H)-CARBOXYLATE IN THE RAT W. LIPPMANN, W. LIPPMANN Ayerst Laboratories, Montreal, Quebec, Canada.Search for more papers by this authorM. WISHNICK, M. WISHNICK Department of Chemical Pharmacology, Lederle Laboratories, American Cyanamid Co., Pearl River, New York, U.S.A.Search for more papers by this author W. LIPPMANN, W. LIPPMANN Ayerst Laboratories, Montreal, Quebec, Canada.Search for more papers by this authorM. WISHNICK, M. WISHNICK Department of Chemical Pharmacology, Lederle Laboratories, American Cyanamid Co., Pearl River, New York, U.S.A.Search for more papers by this author First published: June 1968 https://doi.org/10.1111/j.1476-5381.1968.tb00987.xCitations: 1 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES Bogdanski, D. F., Pletscher, A., Brodie, B. B. & Udenfriend, S. (1956). Identification and assay of serotonin in brain. J. Pharmac. exp. Ther., 117, 82–88. Bray, G. A. (1960). 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Citing Literature Volume33, Issue2June 1968Pages 257-265 ReferencesRelatedInformation

Journal Article Effects of ethyl 3-acetamido-4H-pyrrolo[3, 4-c]-isoxazole-5(6H)carboxylate on tissue levels of catecholamines and 5-hydroxytryptamine in the rat Get access W Lippmann, W Lippmann Department of Chemical Pharmacology, Lederle Laboratories, American Cyanamid Co., Pearl River, New York, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar M Wishnick M Wishnick Department of Chemical Pharmacology, Lederle Laboratories, American Cyanamid Co., Pearl River, New York, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 19, Issue 12, December 1967, Pages 855–856, https://doi.org/10.1111/j.2042-7158.1967.tb09558.x Published: 12 April 2011 Article history Received: 08 August 1967 Published: 12 April 2011

The effects of methotrimeprazine, other phenothiazines and related compounds on the levels of radioactivity and norepinephrine in the hearts of mice after pretreatment with H 3 -norepinephrine have been determined. Administration of methotrimeprazine or normethotrimeprazine at 20 mg/kg i.p. causes a reduction in the radioactivity of the heart after 24 hr, but not after 2.5 hr, and does not prevent the uptake of H 3 - norepinephrine. Chlorpromazine or imipramine causes an increase in the H 3 -catechol content after 24 hr and does block the uptake of H3-norepinephrine. Of the phenothiazines and related compounds tested, some had no effect whereas others cause an increase in the radioactivity after 24 hr. Twenty-four hours after methotrimeprazine administration there is a large decline in the H 3 -catechols with no appreciable change in the endogenous catechol levels. SKF 525A or iproniazid pretreatment interferes with the depleting activity observed. SKF 525A treatment also causes a prolongation of the hypnosis observed after methotrimeprazine administration.

The effects of the administration of epsilon amino caproic acid (EACA) on catecholamine and serotonin levels in the rat and dog were studied. Administration of EACA (500 mg/kg or 2000 mg/kg, orally) causes a depletion of norepinephrine in the rat heart, with several days being required for repletion; EACA at 500 mg/kg has no effect on the catecholamine or serotonin content of the brain or catecholamines in the adrenals. Of the various administered compounds structurally related to EACA none were as active as EACA in causing norepinephrine depletion from the rat heart. 5-Amino-1-pentanol and 6-amino hexanoic acid methyl ester hydrochloride show some depleting activity whereas 6-acetamido hexanoic acid, 6-dimethyl-amino hexanoic acid ethyl ester, 5-amino valeric acid hydrochloride or 6-ureido hexanoic acid show no appreciable activity. Pretreatment of the rat with the monoamine oxidase inhibitor, iproniazid, reduces the decline in norepinephrine content of the heart caused by administered EACA or reserpine. Bretylium prevents completely the depleting action observed after administered EACA or guanethidine and partially that of reserpine. Administered EACA causes a large decline in the endogenous norepinephrine content of the left atrium of the dog and no decrease in the endogenous catecholamines in the adrenals. Subendocardial hemorrhages are observed in EACA- treated dogs. The results obtained with EACA are compared with known depletors of pharmacologic interest.

In the cat brain DL-p-chloro-N-methylamphetamine causes a large decline in the serotonin, and not in neropinephrine concentration, in the hypothalamic area (hypothalamus, hippocampus, and mesencephalon to the intercollicular level) and the diencephalo-thalamic area (caudate and lentiform nuclei and the thalamus) at a dose of 5 mg/kg, intraperitoneally, and after a test period of 16 hours. The serotonin and norepinephrine concentrations of the cortical area (all cortical tissue except hippocampus) were both lowered under these conditions. The preferential action of DL-p-chloro-N-methylamphetamine on the serotonin concentration in the cat brain areas is dose dependent. A large decrease in the serotonin level with only a small one in norepinephrine is observed in the rat brain after intraperitoneal injection of DL-p-chloro-N-methylamphetamine at 26 mg/kg and after 16 hours; there is some decline in the heart norepinephrine under these conditions.