Synthesis and evaluation of substituted 2-phenylcyclobutylamines as analogs of hallucinogenic phenethylamines: lack of LSD-like biological activity
David E. Nichols, K. P. Jadhav, Robert Oberlender, Joseph E. Zabik, Josef F. Bossart, Akihiko Hamada, Duane D. Miller
Journal of Medicinal Chemistry September 1, 1984 DOI: 10.1021/jm00375a004 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 4 5-trimethoxyphenyl)cyclobutylamine trans-2-(2 5-dimethoxy-4-methylphenyl)cyclobutylamine 5-dimethoxy-4-methylphenyl)cyclopropylamine |
| Topics | Mescaline LSD |
| Keywords | Phenethylamines Hallucinogen Biological activity Stereochemistry Pharmacology |
| Citations | 12 |
| Key points | The cyclobutylamine analogues failed to fully substitute for LSD in a drug discrimination test, indicating they are either less potent or produce different subjective effects. |
Abstract
cis- and trans-2-(2,4,5-trimethoxyphenyl)cyclobutylamine and trans-2-(2,5-dimethoxy-4-methylphenyl)cyclobutylamine were synthesized as conformationally restricted analogues of hallucinogenic phenylisopropylamines. In rats trained to discriminate saline from LSD (0.08 mg/kg, ip) in a two-lever drug discrimination paradigm, no generalization of the LSD stimulus to the cis trimethoxy compound occurred at doses up to 20 mg/kg. For both of the trans compounds, partial generalization of the LSD cue occurred at doses of 5 mg/kg or greater. In contrast, complete generalization occurred with trans-2-(2,5-dimethoxy-4-methylphenyl)cyclopropylamine. The ED50 for this compound and the doses of the trans cyclobutyl homologues at which significant drug-appropriate responding occurred indicate that the latter are on the order of 50-75 times less potent than the cyclopropylamine analogue. The lack of generalization to the cyclobutylamines indicates either that their discriminative stimulus properties differ from LSD or that they lack discriminative effects.