Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens

Lyon, Robert A.; Titeler, Milt; Seggel, Mark R.; Glennon, Richard A.

doi:10.1016/0014-2999(88)90432-3

Cited by 51 publications

(33 citation statements)

References 14 publications

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“…5-MeO-DET was fully efficacious at 5-HT 1A and 5-HT 2A receptors. These findings are in agreement with the observation that 5-MeO-DET binds to 5-HT 2 receptors (Lyon et al, 1988) and suggest further that 5-MeO-DET binds to the 5-HT 2A subtype. Taken together, these findings suggest that 5-MeO-DET may have some potential for abuse.…”

Section: Discussionsupporting

confidence: 92%

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Abuse Liability Profile of Three Substituted Tryptamines

Gatch¹,

Forster²,

Janowsky³

et al. 2011

J Pharmacol Exp Ther

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The abuse liability profile of three synthetic hallucinogens, N,Ndiisopropyltryptamine (DIPT), 5-N,N-diethyl-5-methoxytryptamine (5-MeO-DET), and 5-methoxy-␣-methyltryptamine (5-MeO-AMT), was tested in rats trained to discriminate hallucinogenic and psychostimulant compounds, including cocaine, methamphetamine, 3,4-methylenedioxymethylamphetamine (MDMA), lysergic acid diethylamide (LSD), (Ϫ)-2,5-dimethoxy-4-methylamphetamine (DOM), and dimethyltryptamine (DMT). Because abused hallucinogens act at 5-hydroxytryptamine 1A (5-HT 1A ) and 5-HT 2A receptors, and abused psychostimulants act at monoamine transporters, binding and functional activities of DIPT, 5-MeO-DET, and 5-MeO-AMT at these sites were also tested. DIPT fully substituted in rats trained to discriminate DMT (ED 50 ϭ 1.71 mg/kg) and DOM (ED 50 ϭ 1.94 mg/kg), but produced only 68% LSD-appropriate responding. 5-MeO-DET fully substituted for DMT (ED 50 ϭ 0.41 mg/kg) and produced 59% MDMA-appropriate responding. 5-MeO-AMT did not fully substitute for any of the training drugs, but produced 67% LSD-appropriate responding. None of the compounds produced substitution in rats trained to discriminate cocaine or methamphetamine. All three compounds showed activity at 5-HT 1A and 5-HT 2A receptors as well as blockade of reuptake by the serotonin transporter. In addition, 5-MeO-AMT produced low levels of serotonin release and low potency blockade of dopamine uptake. DIPT, 5-MeO-DET, and 5-MeO-AMT produced behavioral and receptor effects similar to those of abused hallucinogens, but were not similar to those of psychostimulants. DIPT and 5-MeO-DET may have abuse liability similar to known hallucinogens and may be hazardous because high doses produced activity and lethality.

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Section: Discussionsupporting

confidence: 92%

“…It also inhibited the reuptake and increased the release of monoamines in brain synaptosomes at micromolar concentrations . Likewise, 5-MeO-DET bound to 5-HT 2 receptors (Lyon et al, 1988) and also inhibited reuptake but did not cause release of monoamines . 5-MeO-AMT lowered intraocular pressure (May et al, 2003).…”

Section: Introductionmentioning

confidence: 93%

Abuse Liability Profile of Three Substituted Tryptamines

Gatch¹,

Forster²,

Janowsky³

et al. 2011

J Pharmacol Exp Ther

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“…3B, Table 3). Lyon et al 23) observed a similar structure-activity relationship for 5-HT 2 receptor binding at this site. In the cases of 2C-C, 2C-I, and 2C-E, the only difference in structure occupies at the 4-position of the aromatic ring, which is substituted with chloride, iodide, and ethyl residues, respectively.…”

Section: Discussionmentioning

confidence: 68%

In Vitro Screening of Psychoactive Drugs by [35S]GTP.GAMMA.S Binding in Rat Brain Membranes

Nonaka

Nagai

Ogata

et al. 2007

Biological & Pharmaceutical Bulletin

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“…(Figure 1). This superimposition makes sense since similar effect-increasing or effect-diminishing influences have been observed at the corresponding places in the two structures in numerous investigations [22,24,25,261.…”

Section: Determination Of the Bioactive Conformationmentioning

confidence: 71%

“…In accordance with Lyon et al [22] and Kang, Johnson and Green [23] the planar six-membered ring systems were superimposed so that position 4 of the tryptamines corresponded to position 1 of the phenylalkanamines, position 5 of the tryptamines to position 2 of the phenylalkanamines etc. (Figure 1).…”

Section: Determination Of the Bioactive Conformationmentioning

confidence: 97%

Three‐dimensional Quantitative Structure–Activity Relationships of Hallucinogenic Phenylalkanamine and Tryptamine Derivatives: Studies using Comparative Molecular Field Analysis (CoMFA)

Beuerle

Kovar

Schulze-Alexandru

1997

Quant. Struct.‐Act. Relat.

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Investigations of the quantitative structure-activity relationships of a data set comprising 66 phenylalkanamines have been carried out using the CoMFA method. This yielded a cross-validated correlation coefficient (q'value) of more than 0.8. The target parameter used was the hallucinogenic effect on humans, since this variable is of particular importance for research into addictive substances. It was possible to confirm the reliability of the CoMFA analysis by using a second, independent phenylalkanamine data set. It was found that models with good predictive properties are obtained if up to ten components are taken into account. In a further step it was possible to include hallucinogenic tryptamine derivatives in a common QSAR analysis with the phenylalkanamines and this in spite of their differing basic structures. The final model from that the CoMFA plots were extracted is based on 148 compounds and permits precise inferences to be made concerning the relationships between structural elements and hallucinogenic effects.

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Indolealkylamine analogs share 5-HT2 binding characteristics with phenylalkylamine hallucinogens

Cited by 51 publications

References 14 publications

Abuse Liability Profile of Three Substituted Tryptamines

Abuse Liability Profile of Three Substituted Tryptamines

In Vitro Screening of Psychoactive Drugs by [35S]GTP.GAMMA.S Binding in Rat Brain Membranes

Three‐dimensional Quantitative Structure–Activity Relationships of Hallucinogenic Phenylalkanamine and Tryptamine Derivatives: Studies using Comparative Molecular Field Analysis (CoMFA)

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