The antinociceptive effects of intrathecally administered cannabinoids are influenced by lipophilicity.
Previous research has demonstrated that intravenously administered cannabinoids produce potent antinociception in rodents. The present study examined the ability of 16 cannabinoid analogs to produce antinociception and hypothermia after intrathecal administration. Fifteen of the compounds tested produced significant increases in the tail-flick response to radiant heat. This effect was stereoselective because N-methyl-dextronantradol, the inactive stereo-isomer of the potent cannabinoid analog N-methyl-levonantradol, failed to elevate tail-flick latencies above baseline values. In general, the drugs tended to be more effective in producing hypothermia than antinociception. A positive correlation found between the ED50 values in producing antinociception and lipophilicity indicated that the most lipid-soluble drugs were the least active. In contrast, no apparent relationship between cannabinoid-induced hypothermia and lipophilicity was found. The finding that the antinociceptive effects of spinally administered cannabinoids is inversely related to lipophilicity is similar to that reported for the opiates.
Lichtman
Aron H
AH
Department of Pharmacology and Toxicology, MCV Station, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298 USA.
Smith
Peter B
PB
Martin
Billy R
BR
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002186:Cannabinoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced; D007278:Injections, Spinal; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010617:Phenanthridines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D012995:Solubility; D013237:Stereoisomerism
D000700:Analgesics; D002186:Cannabinoids; D008055:Lipids; D010617:Phenanthridines; C025490:nantradol