Accession Number : AD0716977

Title :   New Incapacitating Agents. Supplement 3. Preclinical Pharmacology and Toxicology of Candidate Agent 226,169.

Descriptive Note : Quarterly rept. 15/16, 1 Sep 66-10 Jul 67.

Corporate Author : LITTLE (ARTHUR D) INC CAMBRIDGE MASS

Report Date : 10 NOV 1967

Pagination or Media Count : 144

Abstract : The proposed agent, 226,169, has been variously referred to as a nitrogen or alkaloidal analog of tetrahydrocannabinol, an azatetrahydrocannabinol, 'the 3,4-d isomer,' or by its pyridine-derived chemical name, 5,5-dimethyl-10-hydroxy-8-(3-methyl-2-octyl)-2-(2-propynyl) -1,2,3,4-tetrahydro-5H-(1)benzopyrano(3,4-d)pyridine. It was synthesized as part of an effort to determine the effect of introducing a heterocyclic nitrogen atom into the ring of a carbocyclic tetrahydrocannabinol--would it result in agents similar to EA 1476 or, possibly, more potent ones. Although both compounds have similar profiles, in which the principal activity indicates depression of the central nervous system, 226,169 is more potent than EA 1476 in virtually all pharmacological parameters. The nitrogen analog is somewhat more soluble than its carbocyclic counterpart, but poly(ethylene glycol) remains the vehicle of choice for parenteral administration. Cardiovascular (hypotensive) effects are apparent at doses comparable to those producing CNS action. (Author)

Descriptors :   (*INCAPACITATING AGENTS, *PHARMACOLOGY), (*CANNABINOLS, PHARMACOLOGY), TOXICITY, NITROGEN HETEROCYCLIC COMPOUNDS, OXYGEN HETEROCYCLIC COMPOUNDS, CANNABIS, SYNTHESIS(CHEMISTRY), ALKYNES, PHENOLS, MOLECULAR STRUCTURE, HEMATOLOGY, BIOASSAY, PHYSIOLOGY, PSYCHOPHYSIOLOGY, ELECTROPHYSIOLOGY, BEHAVIOR, PATHOLOGY

Subject Categories : Toxicology
      Pharmacology
      Chemical, Biological and Radiological Warfare

Distribution Statement : APPROVED FOR PUBLIC RELEASE