Michael Ross Johnson

Selective and potent analgetics derived from cannabinoids.

Abstract: Based on the hypothesis that analgetic activity is a dissociable feature of the cannabinoid molecule, we examined modifications of the side chain, the phenolic moiety, and, most significantly, structures that lack the benzopyran functionality present in THC and (—)‐9‐nor‐9β‐hydroxyhexahydrocannabinol (HHC). A new grouping, the 1‐methyl‐4‐phenylbutyloxy C‐3 side chain, elaborates a unique lipopholic region. Replacement of the phenol substituent produced several derivatives which retain analgetic activity in the codeine potency range. Introduction of a weakly basic nitrogen at C‐5 and deletion of the axial methyl group in the B ring, two structural changes forbidden by traditional cannabinoid SAR, resulted in a unique family of benzoquinolines with potent analgetic activity. The prototype of this series, levonantradol, exhibits potent and stereospecific analgetic and antiemetic activity.

ONE WAY CROSS TOLERANCE FROM MORPHINE TO NANTRADOL - A POTENT, NON-OPIOID ANALGETIC

Summary Nantradol, a recently described cannabinoid-related analgetic, exhibits potent analgetic, antidiarrheal and antitussive effects in common with opioids. Unlike the opioids, however, nantradols analgetic action is not reversed by the antagonist naloxone. Furthermore, nantradol does not displace 3 H-dihydromorphine and is not discriminated as morphine in rats. However, animals made tolerant to morphine do exhibit one-way analgetic cross tolerance to nantradol. Plasma level determinations indicate that this cross tolerance can not be explained by morphine-induced alterations in pharmacokinetics. These findings, which extend earlier reports of morphine cross tolerance to δ 9 -tetrahydrocannabinol (THC), suggest that opioid and certain cannabinoid analgetics may share a common ultimate mechanism of analgetic action.

4380542 9-hydroxyoctahydrobenzo(c)-quinolines and their pharmaceutical compositions and method of use

1,9-Dihydroxyoctahydrobenzo[c]quinolines (I), 1-hydroxyhexahydrobenzo[c]quinoline-9(8H)-ones (II), and 1-hydroxy-tetrahydrobenzo[c]quinolines (IV) useful as CNS agents, especially as analgesics and tranquilizers, as hypotensives, as agents for the treatment of glaucoma and as diuretics; intermediates therefor (III) and derivatives thereof.