Psychoactive phenylisopropylamines can produce one or more of several different stimulus effects in animals. These effects are typified by the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), the central stimulant amphetamine, and by N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA), an agent whose actions are not yet well understood. The optical isomers of two...
alpha-Ethyltryptamine (alpha-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, alpha-ET substituted for MDMA. These previous studies employed racemic alpha-ET. Because psychoactive...
Certain beta-carbolines are known to be hallucinogenic in humans, and several produce stimulus effects in animals similar to those of the classical hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM). Classical hallucinogens bind at 5-HT2 serotonin receptors and these receptors are thought to play a role in their mechanism of action. In the present study, we examined the binding...
Structurally, methcathinone is to cathinone what methamphetamine is to amphetamine. Due to increased interest in the abuse of such agents we wished to determine if certain derivatives of cathinone would behave in a manner consistent with what is known about their amphetamine counterparts; that is, can amphetamine structure-activity relationships be extrapolated to cathinone analogs? As expected...
The phenylisopropylamine PMMA or N-methyl-1-(4-methoxyphenyl)-2-aminopropane, a structural hybrid of paramethoxyamphetamine (PMA) and methamphetamine, has been previously shown to unexpectedly lack amphetamine-like or hallucinogen-like stimulus properties in animals. For example, in tests of stimulus generalization, neither a (+)amphetamine stimulus nor a DOM stimulus generalized to PMMA. It...
1-(3,4-Methylenedioxyphenyl)-2-aminopropane (MDA) produces an effect in humans that is somewhat similar to both a hallucinogen and a central stimulant. We have previously shown that R(-)-MDA but not S(+)-MDA produces a stimulus effect in animals similar to that of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), whereas S(+)-MDA but not R(-)-MDA produces a stimulus effect...
Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the...
Twenty-two rats were trained to discriminate either 1.5 mg/kg of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a standard two-lever operant procedure. Once responding was stable, various doses of several serotonin (5-HT) antagonists, i.e., cyproheptadine (CYP), methysergide (UML), cinanserin (CIN), and methergoline (MCE), were administered in combination with 5-OMe DMT, to assess...
Rats trained to discriminate either (+)-amphetamine or (+/-)-MDA from saline in a two-lever drug discrimination task, were used to study the stimulus effects of MDA and its two optical isomers. Amphetamine-stimulus generalization occurred to S(+)-MDA, but not to its enantiomer R(-)-MDA. This, coupled with our earlier finding of DOM-stimulus generalization to R(-)-MDA but not to S(+)-MDA,...
Rats trained to discriminate saline from either (+)-amphetamine, (+/-)-DOM, or (+/-)-3,4-MDA in a two-lever drug discrimination paradigm were administered doses of a novel positional isomer of 3,4-MDA, i.e. 2,3-MDA. The novel isomer produced neither amphetamine-appropriate nor DOM-appropriate responding: the 3,4-MDA stimulus did, however, generalize to 2,3-MDA.
The discriminative effects of 5-methoxy-N,N-dimethyltryptamine (5-OMeDMT) were studied in rats trained to discriminate 1.5 mg/kg or 3.0 mg/kg 5-OMeDMT from saline. A series of antagonist and generalization tests revealed that (1) antagonism of the 5-OMeDMT stimulus response by the presumed serotonin antagonist BC-105 depended on the dose of 5-OMeDMT, (2) the 5-OMeDMT stimulus generalized to...
Prominent among the class of hallucinogenic phenylisopropylamines is the 2,5-dimethoxy substitution pattern; this pattern has long been recognized as being an important feature of the more potent agents within this class. The purpose of this present study was to explore the behavioral properties of a series of methoxylated phenylisopropylamines in order to determine the effect of other...
Rats were trained to discriminate injections of either 5-OMe DMT (1.5 mg/kg) or LSD (0.096 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performances were attained (greater than 85%) in each group, dose-response generalizations between the two groups of animals were examined. The results revealed that the 5-OMe DMT-stimulus response generalized to LSD...
Twenty-four rats, trained to discriminate 1.0 mg/kg of (+/-)-DOM, i.e. (+/-)-2,5-dimethoxy-4-methylphenylisopropylamine, from saline under a VI-15 schedule of reinforcement, were challenged with a series of DOM homologs. The agents examined included the 4-ethyl (DOET), -propyl (DOPR), -butyl (DOBU), -tertiary butyl (DOTB) and -amyl (DOAM) derivatives as well as the R(-)- and S(+)-isomers of...
Rats trained to discriminate racemic 2,5-dimethoxy-4-methylphenylisopropylamine, (+/-)-DOM (1.0 mg/kg), from saline in a two-lever drug discrimination task were challenged with the optimal isomers of DOM as well as with several related agents which represent minor molecular modifications of the DOM structure. Generalization of the (+/-)-DOM stimulus was found to occur to R(-)-DOM, S(+)-DOM,...
Rats, trained to discriminate 1.5 mg/kg of the hallucinogenic agent 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a two-lever drug discrimination task, were challenged with various doses of the 4-methoxy, 4-methylthio and 5-methylthio derivatives of DMT. The 5-OMe DMT cue was found to generalize to all three of these agents; the order of potency is 5-OMe greater than 5-SMe greater...
Rats were trained to discriminate injections of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT, 3.0 mg/kg) a hallucinogenic agent for which a serotonergic mechanism has been implicated, from saline in a two-lever drug discrimination task. After reliable levels of accuracy (greater than or equal to 85%) were attained, the ability of the 5-OMe DMT cue to generalize to 36 substituted...
Using an isolated rat fundus preparation, the 4-methyl (DOM), ethyl (DOET), propyl (DOPR) butyl (DOBU), tertiary butyl (DOTB) and amyl (DOAM) derivatives of 2,5-dimethoxy-phenylisopropylamine (2,5-DMA) were found to possess quite similar serotonin receptor affinities (pA2 - 7.02-7.22). The fundus preparation could not be used to determine pD2 values because all of the compounds were found to...
A choice between two levers in an operant chamber was used to train 24 rats, under a variable-interval 15 s schedule of sweetened milk reinforcement, to discriminate a hallucinogenic (psychotomimetic) agent, 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT), from saline administration. The 5-OMe DMT stimulus generalized in a dose-related manner to each of 14 tryptamine related analogs. With the...