PT  - JOURNAL ARTICLE
AU  - Fraser, H. F.
AU  - Isbell, Harris
AU  - Van Horn, Galba D.
TI  - HUMAN PHARMACOLOGY AND ADDICTION LIABILITY OF NORCODEINE
DP  - 1960 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 172--177
VI  - 129
IP  - 2
4099  - http://jpet.aspetjournals.org/content/129/2/172.short
4100  - http://jpet.aspetjournals.org/content/129/2/172.full
SO  - J Pharmacol Exp Ther1960 Jun 01; 129
AB  - Codeine sulfate and norcodeine hydrochloride administered orally have been compared in respect to their human pharmacology and addiction liabilities. In single doses of 75 mg/80 kg orally, both codeine and norcodeine induced mild to moderate morphine-like effects, and as compared to a placebo, both slightly depressed rectal temperature, respiratory rate, respiratory minute-volume, and constricted the pupils. When five successive oral doses of both drugs were given effects again were very similar. When an average of 940 mg of norcodeine daily was substituted orally for morphine in patients addicted to an average of 230 mg of morphine sulfate daily, abstinence was effectively suppressed. In direct addiction tests, tolerance to the intoxicating properties of norcodeine developed more slowly than did tolerance to similar effects of codeine. After 18 days of addiction, the average daily dosage of codeine sulfate attained was 1485 mg, whereas the average dosage of norcodeine hydrochloride was only 400 mg. After 30 to 45 days of addiction to either codeine or norcodeine, 3 mg of nalorphine precipitated mild to moderate abstinence. When norcodeine and codeine were discontinued abruptly after 60 days of addiction, the abstinence syndrome which developed was much milder after withdrawal of norcodeine than after withdrawal of codeine. Norcodeine possesses addictive properties, but these are significantly less than those of codeine in respect to the degree of physical dependence which develops.