The benzodiazepine derivatives exert many actions on the central nervous and cardiovascular systems that are characteristic of the sedative-hypnotics. 7 The compound lorazepam [7-chloro-5-( o-chlorophenyl) -1,3,dihyro-3-hydroxy-2H-l,4-benzodiazepin-2-one], which differs from oxazepam only in that it has CI in the ortho position on the 5-phenyl ring, has shown in experimental animals pharmacologic properties comparable to those of others in the benzodiazepine series (Formula 1), e.g., as an antianxiety agent, it is 20 times as potent and as an anticonvulsant it is 10 to 50 times as active as chlordiazepoxide.1I
The effects of heroin given to human subjects by continuous intravenous infusion are described. Progressive CNS depression eventually required reversal with levallorphan. There was no indication of development of acute tolerance to the depressant effects of heroin. Blood and urine specimens were collected for analysis of metabolites and analyzed for morphine, 6‐monoacetylmorphine, and heroin by gas‐liquid chromatography. Blood concentrations were too low to identify any heroin or metabolites, but about fifty per cent of the dose was recovered in the urine mostly as bound morphine with small amounts of 6‐monoacetylmorphine and heroin present in some specimens. Rate of excretion of total morphine indicated that man can metabolize about 6 mg. per 93 Kg. per hour of heroin.
Miosis produced by codeine is not antagonized by nalorphine until large oral doses are administered for several days. The present experiment was conducted in order to further study this characteristic of the codeine effect. Eight healthy male volunteers, who were former drug users, were divided into two groups. Subjects in the first group were given a continuous infusion of codeine, 30 mg/hr for 11-16 hr. No subjective effects were reported by the volunteers. In three of the individuals definite miosis antagonized by nalorphine was observed at 9.5 hr. The dose of codeine for the second group was 60 mg/hr for 11 hr. Mild but definite subjective effects were experienced by each of the participants in this group. Miosis appeared between 2 and 6 hr. Challenges at 4 and 6 hr were positive in two subjects and negative or equivocal in the other two. Codeine was excreted in the urine as free and conjugated codeine, morphine, and norcodeine. Maximum rates of excretion were similar for both groups, suggesting that the maximum amount of codeine that can be metabolized is equal or less than 30 mg/hr. Also codeine clearance, being greater than creatinine clearance, suggests that codeine might be excreted by glomerular filtration and tubular secretion. Blood levels of codeine in the 60 mg/hr group were about 10 times those reported as therapeutic. However, morphine or norcodeine were not detectable by the methods used.
Several parameters of the nalorphine test for narcotic use were evaluated in prisoners with histories of prior narcotic use. Measurement of changes in pupillary diameter caused by narcotics alone or in combination with narcotic antagonists was correlated with chemical analysis of the urine for narcotics or metabolites. After one dose of morphine, the pupillary test remained positive about 4 hours, while urinalysis usually detected a single dose for as long as 36 hours. However, when morphine was administered every 6 hours for 5 days, some sub;ects gave positive pupillary tests 20 hours after the last dose. Negative pupillary tests were obtained after as many as three doses of codeine, but when codeine was given every 6 hours for 5 days more positive tests were obtained each day. Positive pupillary tests were obtained 2 to 4 hours after single in;ections of meperidine, heroin, and oxycodone, and 6 hours after methadone. The pupillary test is a useful method of screening for narcotic use, which might well be combined with chemical tests for narcotics in the urine.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.