The discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): Differentiation from amphetamine

Silverman, Peter B.; Ho, Beng T.

doi:10.1007/bf00428105

Cited by 53 publications

(22 citation statements)

References 25 publications

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“…The discriminative stimulus effects of DOM and other 5-HT 2A receptor agonists have been studied extensively in rats (Silverman and Ho, 1980;Glennon et al, 1982Glennon et al, , 1983Fiorella et al, 1995;Li et al, 2007) and much less in nonhuman primates (Li et al, 2008). Consistent with those studies, discriminative stimulus effects of DOM in this study were pharmacologically selective with other compounds failing to occasion substantial responding on the DOM-associated lever.…”

Section: Discussionsupporting

confidence: 82%

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM), Ketanserin, and (R)-(+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907) in Rats

Unzeitig

Javors³

et al. 2009

J Pharmacol Exp Ther

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Very little is known about constitutive activity in vivo. This study examined whether constitutive activity and inverse agonism contribute to discriminative stimulus effects of drugs acting at serotonin (5-HT) 2A receptors. Rats were trained to discriminate between saline and either 0.56 mg/kg 5-HT 2 receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), 1.0 mg/kg 5-HT 2A receptor antagonist ketanserin, or 0.1 mg/kg purported 5-HT 2A receptor inverse agonist (R)-(ϩ)-␣-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907). Discriminative control was established with each drug after 33 to 35 sessions. MDL100907 and ketanserin did not occasion DOM lever responding but attenuated the discriminative stimulus effects of DOM. DOM did not occasion responding on the drug-associated lever in rats discriminating MDL100907 or ketanserin, but attenuated the discriminative stimulus effects of both drugs. Ketanserin and ritanserin occasioned MDL100907-lever responding, whereas rats discriminating ketanserin responded only partially on the drugassociated lever after receiving MDL100907, ritanserin, or the ␣ 1 -adrenergic antagonist prazosin. Combining prazosin with MDL100907 or ritanserin resulted in near-complete ketanserinlever responding, indicating that the ketanserin stimulus involves both 5-HT 2A and ␣ 1 -adrenergic receptors. Administration of p-chlorophenylalanine methyl ester, then fenfluramine, significantly decreased cortical 5-HT, enhanced sensitivity to the discriminative stimulus effects of DOM, and occasioned partial MDL100907-lever responding. Collectively, these results show that DOM and MDL100907 discriminative stimulus effects are mediated by 5-HT 2A receptors and that ketanserin discriminative stimulus effects involve both 5-HT 2A and ␣ 1 -adrenergic receptors. Results in 5-HT-depleted rats further suggest that the discriminative stimulus effects of MDL100907 might involve antagonism of endogenous 5-HT and/or inverse agonism at 5-HT 2A receptors.In classic receptor theory, receptor ligands are characterized by affinity and intrinsic activity (Ariens, 1954), with the latter varying from no (zero) activity (i.e., antagonist) to high activity (efficacy; e.g., full agonist). Two observations prompted revision of this conceptualization of ligand/receptor interactions. First, under some conditions receptor signaling occurs in the absence of ligand binding, suggesting constitutive activity of unbound receptors. Second, some drugs that are presumed to be antagonists (zero efficacy) decrease receptor signaling that occurs in the absence of endogenous or exogenous agonist. Thus, a third class of receptor ligands was proposed-inverse agonists (Kenakin, 1996;Strange 2000;Costa and Herz, 1989;Parra and Bond, 2007); in a constitutively active (i.e., ligand-independent) system, receptor signaling is increased by agonists, decreased by inverse agonists, and not affected by antagonists.Serotonin (5-HT) 2 receptors are constitutively active under some conditions (for review...

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Section: Discussionsupporting

confidence: 82%

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM), Ketanserin, and (R)-(+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907) in Rats

Unzeitig

Javors³

et al. 2009

J Pharmacol Exp Ther

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“…In stimulus antagonism studies, the ( + )-amphetamine-stimulus was not attenuated by cinanserin",2s or methysergide. In animals trained to discriminate ( + )-amphetamine from vehicle under DRL, tandem, and FR schedules of reinforcement, stimulus generalization has been reported to occur to cocaine,7,'6'19,21,24,32 b ut not to p-hydroxyamphetamine.7,3',3.5 Under DRL, tandem, and VI schedules, however, no generalization, or partial generalization, has been observed with 2,5-DMA7, 28,55 and DOM. 728, 40 In stimulus antagonism studies, the ( + )-amphetamine-stim- …”

Section: Comparisons With Different Operant Schedulesmentioning

confidence: 96%

“…PEA' (8) 4-OH PIAh (5,25,35) (-)-DOM (13,28) MMA* (7) "Each entry is followed by the appropriate literature citation in parenthesis. See Tables I and 11 for dose of training drug, animal species, route of administration, etc.…”

Section: Cmentioning

confidence: 99%

Discriminative stimulus properties of amphetamine and structurally related phenalkylamines

Young¹,

Glennon

1986

Medicinal Research Reviews

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“…Drug discrimination procedures have been used to study a wide variety of drugs, including the well known hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) (Glennon et al,1983a;Silverman and Ho, 1980). Several studies have established stimulus control with DOM in rats and examined the structure-activity relationships for various drugs acting on serotonergic (5-HT) systems (for reviews, see Glennon et al, 1983b;Glennon, 1988;Winter et al, 1999).…”

mentioning

confidence: 99%

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane in Rhesus Monkeys

Rice

2007

J Pharmacol Exp Ther

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Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and related drugs have been studied extensively in rodents, although the generality of those findings across species is not known. The goals of this study were to see whether monkeys could discriminate DOM and to characterize the DOM discriminative stimulus by studying a variety of drugs, including those with hallucinogenic activity in humans. Four rhesus monkeys discriminated between 0.32 mg/kg s.c. DOM and vehicle after an average of 116 (range ϭ 85-166) sessions while responding under a fixed ratio 5 schedule of stimulus shock termination.

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The discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): Differentiation from amphetamine

Cited by 53 publications

References 25 publications

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM), Ketanserin, and (R)-(+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907) in Rats

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM), Ketanserin, and (R)-(+)-α-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907) in Rats

Discriminative stimulus properties of amphetamine and structurally related phenalkylamines

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane in Rhesus Monkeys

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