Levels and distribution of central nervous system amines in normal and morphine-dependent monkeys

The distribution of norepinephrine, dopamine and 5-hydroxytryptamine in various areas of the CNS of the normal monkey has been presented.The central levels and distribution of norepinephrine, dopamine and 5-hydroxytryptamine were determined after single doses of morphine, during maintenance of physical dependence and following withdrawal from chronic administration of morphine. Small and non-stressful doses of morphine were employed to induce experimental physical dependence.Alpha-methyl-DOPA did not qualitatively or quantitatively alter the abstinence syndrome.Pretreatment with iproniazid did not prevent depression produced by single doses of morphine in the non-tolerant monkey.The data observed in this study offer no support for the view that gross behavioral changes in the monkey produced by morphine or by its withdrawal after the development of physical dependence are induced by or may be correlated with changes in amine levels in the CNS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34146/1/0000431.pd

Relationship of the structure of mescaline and seven analogs to toxicity and behavior in five species of laboratory animals

The effect of mescaline and of 7 mescaline analogs (3,4-dimethoxy-[beta]-phenylethylamine; 3,4-methylenedioxy-[beta]-phenylethylamine; 3,4-methylenedioxy-[alpha]-methyl-[beta]-phenylethylamine; 3,4-methylenedioxy-[alpha]-ethyl-[beta]-phenylethylamine; 3,4-dimethoxy-[alpha]-methyl-[beta]-phenylethylamine; 3,4,5-trimethoxy-[alpha]-methyl-[beta]-phenylethylamine; and 3,4-methylenedioxy-N,[alpha]-dimethyl-[beta]-phenylethylamine) has been studied in the mouse, rat and guinea pig following ip administration and in the mongrel dog and rhesus monkey following iv administration. The LD50 value for each agent has been determined in each species. For 7 of the 8 drugs tested the LD50 value is significantly lower in the rat than in the mouse or guinea pig. A comparison of the observable signs of drug action in the dog and monkey shows the dog to be the preferred species for evaluating the effects of these agents. The relevant literature regarding the actions of the drugs has been reviewed. Modifications in the mescaline structure which are represented by the 7 analogs and which alter pharmacologic activity include: decreased potency following removal of the 5-methoxy group or N-demethylation, and increased potency following alpha substitution on the side chain or introduction of the 3,4-methylenedioxy group.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33868/1/0000129.pd

A comparison of the pharmacology of two potent analgesic agents, piminodine (Win 14,098-2) and Win 13,797, with morphine and meperidine

The toxic and lethal effects of piminodine and Win 13,797 were studied in mice, dogs, and monkeys. The analgesic actions of both drugs were tested in mice and rats and were found to be more potent than morphine.Vascular studies on pimincdine and Win 13,797 have shown peripheral vasodilation and acute vascular tolerance to the hypotensive effect in dogs with partial crossed tolerance to morphine. Dogs anesthetized with pentobarbital were sensitive to the respiratory depressant actions of these drugs. Nalorphine readily antagonizes this respiratory depression.Piminodine and Win 13,797 are myocardial depressants on the dog heart-lung preparation and the cat papillary muscle, but only in doses or concentrations much higher than would be used therapeutically.The actions of piminodine and Win 13,797 on the isolated rabbit jejunal segment are minimal.The qualitative actions of piminodine and Win 13,797 on EEG effects in dogs with chronically implanted electrodes were like those of morphine. Quantitatively, Win 13,797 was equipotent to morphine, and piminodine one-half as effective.Studies on single-dose suppression in monkey and primary physical dependence in dogs and monkeys indicate that piminodine and Win 13,797 have high addiction liability at least in these species.Nearly all the administered piminodine or Win 13,797 is altered chemically when injected into dogs. There is no evidence for marked local tissue deposition for either drug.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32367/1/0000442.pd

ANIMAL EXPERIMENTATION IN STUDYING ADDICTION TO THE NEWER SYNTHETIC ANALGESICS

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71458/1/j.1749-6632.1948.tb27253.x.pd

Editorial Consultant Editorial Consultant

iv Foreword Since the turn of the century, scientists have become increasingly interested in the effects of tobacco on health. Only within the past few decades, however, has a broad experimental and clinical approach to the subject been manifest; within this period the most extensive and definitive studies have been undertaken since 1950. Few medical questions have stirred such public interest or created more scientific debate than the tobacco-health controversy. The interrelationships of smoking and health undoubtedly are complex. The subject does not lend itself to easy answers. Nevertheless, it has been increasingly apparent that answers must be found. As the principal Federal agency concerned broadly with the health of the American people, the Public Health Service has been conscious of its deep responsibility for seeking these answers. As steps in that direction it has seemed necessary to determine, as precisely as possible, the direction o