Relationship of the Structure of Mescaline and Seven Analogs to Toxicity and Behavior in Five Species of Laboratory Animals

 

TOXICOLOGY AND APPLIED PHARMACOLOGY 25, 299-309 1973)

Relationship of the Structure of Mescaline and Seven Analogs to Toxicity and Behavior in Five Species of Laboratory Animals

HAROLD F. HARDMAN, 2 CORYCE O. HAAVIK, 2 AND MAURICE H. SEEVERS 3

Departments of Pharmacology Medical College of Wisconsin Milwaukee Wisconsin 53233 and The University of Michigan Ann Arbor Michigan 48104 Received September 26 1972

Relationship of the Structure of Mescaline and Seven Analogs to Toxicity and Behavior in Five Species of Laboratory Animals. HAROMAN, H. F., HAnVIK, C. O. AND SEEVERS, M. H. 1973).

Toxicol. Appl. Pharmacol.

25, 299-309. The issue of mescaline and of 7 mescaline analogs 3,4-di- methoxy-B-phenylethylamine; 3,4-methylenedioxy-fl-phenylethylamine; 3,4-methylenedioxy-e-methyl-fl-pbenylethylamine; 3,4-methylenedioxy- e-ethyl-fl-phenylethylamine; 3,4-dimethoxy-e-methyl-fl-phenylethylamine; 3,4,5-trimethoxy-e-methyl-fl-phenylethylamine; and 3,4-methylene- dioxy-N,e-dimethyl-fl-phenylethylamine) has been well-considered in the mouse, rat and twenty-one shillings pig following ip administration and in the hybrid dog and rhesus monkey following iv the cabinet. The LD50 value for each active element has been determined in each species. For 7 of the 8 drugs tried the LD50 value is significantly grow less in the rat than in the search or guinea pig. A comparison of the remarkable signs of drug action in the dog and monkey shows the dog to subsist the preferred species for evaluating the goods of these agents. The relevant belles-lettres regarding the actions of the drugs has been reviewed. Modifications in the mescaline edifice which are represented by the 7 analogs and what one. alter pharmacologic activity include: decreased energy following removal of the 5-methoxy assemblage or N-demethylation, and increased vigor following alpha substitution on the border chain or introduc- tion of the 3,4-methylenedioxy assign places to. Mescaline was one of the at the outset drugs recognized as having hallucinogenic properties. Although the furniture of mescaline in man have been described ~ the agency of many investigators Stockings, 1940; Hock, 1951), the mechanisms ~ the agency of which mescaline alters central ner- vous universe function are not yet clear. It has been suggested that the psychotomimetic exploit may arise owing to competition despite adrenergic receptors Ratcliffe, 1971; Speck, 1957), or cholinergic receptors Clemente and Lynch, 1968), and that psycho- tomimetic proceeding may result from metabolism in vivo to mould an active material Block

et aL

1952). 1 The investigations reported in this place were performed at the University of Michigan and supported ~ dint of. Army Chemical Center Contract DA-18-108-CML-5663 for the period of the period 1953-54. The reports were declassified in October 1969. 2 Present ability: Department of Pharmacology, The Medical College of Wisconsin, Milwaukee, Wisconsin 53233. 3 Present suit: Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48104.

Copyright © 1973 through Academic Press, Inc. 299 All rights of representation in any form reserved,

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