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.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 3
- Structure–activity relationships of serotonin 5‐HT2Aagonists Wiley Interdisciplinary Reviews Membrane Transport and Signalling February 28, 2012
- Hallucinogens. Pharmacology & Therapeutics February 1, 2004
- Studies of the relationship between molecular structure and hallucinogenic activity. Pharmacology, Biochemistry, and Behavior February 1986