Life sciences
December 17, 1984
R A Glennon, M Titeler, J D Mckenney
636 citations
The hallucinogenic potency of psychoactive agents, including LSD and related compounds, is closely linked to their ability to bind to 5-HT2 receptors in the brain. Binding affinities for 5-HT2 sites strongly correlated with both behavioral effects in animals (r = 0.938) and hallucinogenic potency in humans (r = 0.924). These findings indicate that activation of 5-HT2 receptors is a key mechanism underlying the hallucinogenic effects of these substances.
Pharmacology, biochemistry, and behavior
August 1, 1990
N A Darmani, B R Martin, U Pandey et al.
245 citations
In mice, the drug (+/-)-DOI, which activates 5-HT2 receptors, causes a head-twitch response that increases with dose. The (-) isomer of DOI is twice as potent as the (+) isomer. Selective 5-HT2 blockers (ketanserin and spiperone) reduce this response in a dose-dependent way. A nonselective 5-HT agonist (5-MeO DMT) and a 5-HT1A-selective agonist (8-OH-DPAT) also reduce the response, but a 5-HT1B/5-HT1C-selective agonist (TFMPP) does not. The authors propose that 5-HT1A receptors inhibit the 5-HT2 receptor-mediated head-twitch response.
Pharmacology, biochemistry, and behavior
January 1, 1997
R A Glennon, R Young, M Dukat et al.
48 citations
The drug PMMA, a hybrid of PMA and methamphetamine, produces effects in rats similar to MDMA (Ecstasy) but lacks the stimulant or hallucinogen-like properties of amphetamine or DOM. Rats trained to distinguish PMMA from saline did not respond to amphetamine or DOM, but did respond to MDMA and its S(+) isomer. Partial responses occurred with several related compounds. These results suggest PMMA acts like MDMA without amphetamine-like stimulation, supporting the idea that PMMA is the structural parent of MDMA-like designer drugs.
Pharmacology, biochemistry, and behavior
March 1, 1992
N A Darmani, B R Martin, R A Glennon
48 citations
Cocaine acutely suppresses a serotonin-related behavior in mice (the head-twitch response) by activating other receptors, not by blocking 5-HT3 receptors. During withdrawal from chronic cocaine treatment, the same behavior becomes enhanced, indicating supersensitivity that can last up to 172 hours depending on the cocaine dose. Low-dose chronic cocaine withdrawal increases the response to a selective 5-HT2 agonist, while higher doses do not. Withdrawal also increases the inhibitory effect of a 5-HT1A agonist on the behavior.
Psychopharmacology
January 1, 1980
R A Glennon, R Young, J A Rosecrans et al.
46 citations
Rats can be trained to distinguish the hallucinogenic drug 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from a saline placebo using a lever-choice task. Once trained, the rats responded to 14 chemically similar tryptamine compounds as if they were 5-OMe DMT, with the strength of this response depending on the dose. For all but one compound, the dose needed to produce the drug-like response was strongly correlated (r = -0.86) with how tightly the compound binds to serotonin (5-HT) receptors, suggesting that these drugs' hallucinogenic effects are mediated through the serotonin system.
Life sciences
June 14, 1982
R Young, J A Rosecrans, R A Glennon
26 citations
Rats trained to distinguish injections of 5-OMe DMT or LSD from saline showed that the effects of these drugs are interchangeable: animals trained on one drug recognized the other. The serotonin antagonist BC-105 reduced the effects of both drugs, but the pattern of this reduction differed between them, suggesting that while both drugs act through the serotonin system, they interact with it in somewhat different ways.
Psychopharmacology
January 1, 1983
R Young, J A Rosecrans, R A Glennon
25 citations
In rats, the drug 5-OMeDMT produces discriminative effects that generalize to LSD, and both effects are blocked by the serotonin antagonist BC-105 in a dose-dependent manner. When rats responded for food under a variable-interval schedule, 1.0-3.0 mg/kg of 5-OMeDMT decreased response rates. BC-105 blocked the rate decrease from 1.5 mg/kg but not from 3.0 mg/kg, even though both doses alone reduced responding equally. These findings show that the dose of 5-OMeDMT critically determines whether antagonism occurs.
European journal of pharmacology
December 17, 1981
R A Glennon, J A Rosecrans, R Young
21 citations
Rats learned to distinguish an injection of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a two-lever drug discrimination task. Once they reliably identified the drug, 36 different phenylisopropylamine compounds were tested to see if they produced similar effects. The compounds fell into three groups: those that fully mimicked 5-OMe DMT, those that partially did, and those that did not. The findings suggest that certain phenylisopropylamines, unlike amphetamine, can produce hallucinogen-like effects in rats, likely involving serotonin pathways.
Journal of medicinal chemistry
November 1, 1979
R A Glennon, P K Gessner, D D Godse et al.
17 citations
Bufotenine, a psychoactive compound, has weak behavioral effects in humans and animals, likely because it cannot easily cross the blood-brain barrier. Researchers synthesized several ester derivatives of bufotenine to evaluate them pharmacologically. Unexpectedly, all the esters showed strong affinity for serotonin receptors in isolated rat stomach tissue. Chromatographic analysis indicated that the esters were not extensively broken down into bufotenine during the assay, suggesting the esters themselves may be active at these receptors.
Pharmacology, biochemistry, and behavior
January 1, 2001
J B Rangisetty, M L Bondarev, J Chang-Fong et al.
14 citations
Psychoactive phenylisopropylamines can produce different stimulus effects in animals, typified by hallucinogen DOM, stimulant amphetamine, and the less understood agent PMMA. In rats trained to discriminate PMMA from vehicle, the PMMA stimulus generalized to both optical isomers of MBDB and 3,4-DMA, with S(+)-MBDB (ED50=0.8 mg/kg) more potent than R(-)-MBDB (2.0 mg/kg) and S(+)-3,4-DMA (2.6 mg/kg) more potent than R(-)-3,4-DMA (3.9 mg/kg). These agents produce stimulus effects similar to PMMA. Both isomers of 3,4-DMA substituted for an MDMA stimulus but not for DOM or amphetamine stimuli. The evidence suggests PMMA, both isomers of MBDB and 3,4-DMA, and S(+)-MDMA produce common stimulus effects in rats, better defining the PMMA stimulus and structural requirements for this effect.
Pharmacology, biochemistry, and behavior
December 1, 1986
R Young, J A Rosecrans, R A Glennon
10 citations
In rats trained to distinguish the psychedelic compound 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline, the serotonin antagonist cyproheptadine completely blocked the drug's effects at a low dose, while cinanserin and methergoline partially blocked them, and methysergide had little effect. At a higher dose of 5-OMe DMT, methysergide and methergoline partially blocked the drug's effects, but cyproheptadine and cinanserin did not. The authors advise caution when drawing conclusions from studies using these drugs until their in vivo effects and mechanisms are better understood.
Life sciences
February 1, 1982
R A Glennon, R Young, F Benington et al.
8 citations
Rats trained to distinguish the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a drug discrimination task were tested with three related compounds: the 4-methoxy, 4-methylthio, and 5-methylthio derivatives of DMT. All three derivatives produced effects similar to the original drug. The relative potency of the compounds, from most to least potent, was 5-OMe DMT, followed by 5-SMe DMT, then 4-OMe DMT, and finally 4-SMe DMT.