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Derivatives of apomorphine and of N‐n‐propylnorapomorphine were prepared to obtain modified pharmacological activity and enhanced chemical stability. Mouse profile and dog emesis screens were performed, and the activity of various N‐substituted derivatives and their esters was evaluated and compared to the parent compounds. The N‐n‐propyl diacetate derivative and N‐methyl and N‐n‐propyl ascorbate salts were remarkably stable to air; apomorphine etherate was no more stable than the free base. The dimers, the major products formed during the acid‐catalyzed rearrangement of morphines to apomorphines, were all potent emetics. Additionally, two showed a significant antagonism to morphine in mice and dogs.

2,5-Dimethyl-2′-hydroxy-9α-(3-methylbutyl)-6,7-benzomorphan, the 9β-analogue, and 9α-N-substituted (N-ethyl, propyl, butyl, pentyl, hexyl, phenylethyl, allyl, and cyclopropylmethyl) compounds were synthesized and evaluated biochemically and pharmacologically. The 9β N-methyl compound was found to be as potent as morphine in the mouse hot plate assay and had one-seventh the affinity of morphine for the opioid receptor. The N-alkyl and N-phenethyl 9α-substituted compounds were either inactive or relatively ineffective as antinociceptive agents. None of the examined compounds substituted for morphine in single-dose suppression studies in the rhesus monkey. The N-cyclopropylmethyl compound in the 9αseries had half the narcotic antagonist potency of nalorphine and one-eighth of its affinity for the opioid receptor. The 9α-(3-methylbutyl) moiety, unlike bulky substituents in the 9βposition of 6,7-benzomorphans, generally lowers affinity for the μ opioid receptor and diminishes their in vivo activity as agonists or antagonists.

Tritiated Δ9-tetrahydrocannabinol (I) was administered both orally and intravenously to groups of bile duct-cannulated rats and those with their bile duct intact. From 55.8 to 66.9% of the total radioactivity was excreted during the 96-hr. period following administration. The excretion of radioactivity was minimal in each group beyond 48hr. after drug administration. The major route of excretion following the intravenous administration in bile duct-cannulated rats was by way of bile (59.4%; feces, 2.7%), whereas more radioactivity was excreted in feces (41.5%) than bile (21.5%) when the drug was given orally. The radioactivity excreted in the feces of the orally medicated rats was mainly extractable in petroleum ether. This extract was found to contain I by TLC and GLC analysis. After intravenous administration, the radioactivity in the feces was not extractable in petroleum ether but appeared in ether, methanol, and water extracts. TLC confirmed that the radioactivity in these solvents was associated with metabolites of I. Bile contained mainly metabolites of I, as did the urine. Less than 10% of the radioactivity was excreted in the urine of each group of rats.

An extract of Cannabis sativaL. root yielded two pentacyclic triterpenes, friedelin and epifriedelanol, and N-(p-hydroxy-β-phenylethyl)-p-hydroxy-trans-cinnamamide. Structures of the triterpenes were confirmed by preparation of derivatives and comparison to authentic friedelin. Epifriedelanol was also oxidized to friedelin. The amide was confirmed by synthesis.