The present study investigated interactions between the novel psychoactive tryptamines DiPT, 4-OH-DiPT, 4-OH-MET, 5-MeO-AMT, and 5-MeO-MiPT at monoamine receptors and transporters compared with the classic hallucinogens lysergic acid diethylamide (LSD), psilocin, N,N-dimethyltryptamine (DMT), and mescaline. We investigated binding affinities at human monoami...
Studies have shown that both serotonin and glutamate receptor systems play a crucial role in the mechanisms underlying drug-induced synesthesia. The specific nature of these mechanisms, however, continues to remain elusive. Here we propose two distinct hypotheses for how synesthesia triggered by hallucinogens in the serotonin-agonist family may occur. One hy...
Hallucinogens have been part of spiritual practice for millennia, but controversy surrounding their mind-manifesting effects led to their proscription by the mid-20th century, largely without evidence of harm or toxicity and despite nascent data suggesting therapeutic utility in treating depressive illnesses. This review explores their pharmacodynamic action...
Though synesthesia research has seen a huge growth in recent decades, and tremendous progress has been made in terms of understanding the mechanism and cause of synesthesia, we are still left mostly in the dark when it comes to the mechanistic commonalities (if any) among developmental, acquired and drug-induced synesthesia. We know that many forms of synest...
Human UDP-glucuronosyltransferases (UGTs) are important in the metabolic elimination of xenobiotics and endogenous compounds from the body. These enzymes transfer glucuronic acid moiety from the cosubstrate, UDP-glucuronic acid (UDPGA), to nucleophilic groups of small organic molecules, such as hydroxyl, carboxylic, or amino group. The conjugation of these m...
Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hall...
Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects t...
RationaleTrifluoromethylphenyl piperazine (TFMPP) is an active constituent of a relatively new group of recreational drugs known as 'party pills'. TFMPP has been anecdotally reported to induce mild psychedelic effects similar to lysergic acid diethylamide and psilocybin. There has been no research about the subjective effects of TFMPP in humans.ObjectivesThi...
A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This appr...
We used the MembStruk computational procedure to predict the three-dimensional (3D) structure for the serotonin 5-HT(2C) G-protein-coupled receptor (GPCR). Using this structure, we used the MSCDock computational procedure to predict the 3D structures for bound ligand-protein complexes for agonists such as serotonin and antagonists such as ritanserin, metergo...
The psychosis associated with schizophrenia is characterized by alterations in sensory processing and perception. Some antipsychotic drugs were identified by their high affinity for serotonin 5-HT2A receptors (2AR). Drugs that interact with metabotropic glutamate receptors (mGluR) also have potential for the treatment of schizophrenia. The effects of halluci...
Hallucinogens, including mescaline, psilocybin, and lysergic acid diethylamide (LSD), profoundly affect perception, cognition, and mood. All known drugs of this class are 5-HT(2A) receptor (2AR) agonists, yet closely related 2AR agonists such as lisuride lack comparable psychoactive properties. Why only certain 2AR agonists are hallucinogens and which neural...
A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activa...
A review of the neuropharmacology of the alleged hallucinogen bufotenine is presented, including recent experimental results showing activity similar to LSD and other known hallucinogens (psilocin and 5-MeO-DMT) at the purported hallucinogenic serotonin (5-HT) receptors, 5-HT2A and 5-HT2C. In addition, current reports of computer modeling of the receptors an...
The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+/-)-3-(N-Methylpyrrolidin-3-yl)...
The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psiloc...
An important determinant of the neurobehavioral responses induced by a drug is its relative receptor selectivity. The molecular basis of ligand selectivity of hallucinogenic and nonhallucinogenic compounds of varying structural classes for the human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors was investigated with the use of reciprocal site-directed mu...
To date, there is no doubt that dopamine plays a key role in the behavioural disorders associated with schizophrenia. However, dopamine is not the only neurotransmitter involved in this syndrome, as it interacts with many neuronal systems in brain. Of special interest is the interaction between dopaminergic and serotoninergic systems with evidence from pharm...
A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a...
In blood platelets of rabbits, the shape change-inducing effect of D-lysergic acid diethylamide (D-LSD) has been compared with the D-LSD-binding. D-LSD, but not L-LSD, caused a shape change reaction (EC50 1.3 x 10(-9) M) which was inhibited by various 5-HT antagonists (methergoline and neuroleptic drugs), butaclamol showing marked stereospecificity. Strong i...
