New Incapacitating Agents. Supplement 3. Preclinical Pharmacology and Toxicology of Candidate Agent 226,169.
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)
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 10, 1967
- Accession Number
- AD0716977
Entities
Organizations
- Arthur D. Little