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Related Concept Videos

CNS Stimulants: Psychedelic Agents01:22

CNS Stimulants: Psychedelic Agents

Hallucinogens, also known as psychedelic drugs, are a class of substances known for their ability to alter perception, cognition, and emotions. Despite their profound effects on the mind, these drugs are non-addictive, setting them apart from many other abused substances. The mechanism of action of these drugs lies in their impact on the 5-HT2A receptor in the brain. Upon activation, this receptor couples to Gq-type G proteins, triggering a cascade that releases intracellular calcium. This...
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Hallucinogens and Psychedelics01:27

Hallucinogens and Psychedelics

Hallucinogens are psychoactive substances that profoundly alter perceptual experiences, generating unreal visual and sensory images. Often referred to as psychedelic drugs — a term derived from the Greek words "psyche" (mind) and "delos" (revealing) — these substances include marijuana and lysergic acid diethylamide (LSD), among others. These drugs vary in intensity and effects.
Marijuana, derived from the dried leaves and flowers of the hemp plant, contains delta-9-tetrahydrocannabinol (THC)...
Adrenergic Agonists: Indirect-Acting Agents01:25

Adrenergic Agonists: Indirect-Acting Agents

Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Drugs Affecting Neurotransmitter Release or Uptake01:21

Drugs Affecting Neurotransmitter Release or Uptake

Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
Antipsychotic Drugs: Typical and Atypical Agents01:21

Antipsychotic Drugs: Typical and Atypical Agents

Antipsychotic drugs are classified into first-generation (typical) drugs including phenothiazines; and second-generation (atypical) drugs. Chlorpromazine hydrochloride (Thorazine), a phenothiazine derivative, broadly impacts the central, autonomic, and endocrine systems. This drug, along with typical agents like haloperidol (Haldol), primarily works by antagonizing D2 receptors, thus reducing dopaminergic neurotransmission. However, typical antipsychotics can cause side effects such as sedation...

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Agonist-trafficking and hallucinogens.

Javier González-Maeso1, Stuart C Sealfon

  • 1Departments of Psychiatry, Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. Javier.Maeso@mssm.edu

Current Medicinal Chemistry
|March 12, 2009
PubMed
Summary

G protein-coupled receptors (GPCRs) activate distinct signaling pathways based on agonist-bound conformations. This agonist-trafficking model explains how hallucinogenic drugs like LSD affect serotonin 5-HT2A receptors (5-HT2ARs) differently than non-hallucinogenic compounds.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Molecular Biology

Background:

  • G protein-coupled receptors (GPCRs) are key drug targets, traditionally modeled by the ternary complex model.
  • The ternary complex model describes GPCRs in equilibrium between active and inactive states.
  • Evidence suggests agonists stabilize distinct GPCR conformations, leading to biased signaling.

Purpose of the Study:

  • To review current knowledge on agonist-trafficking at GPCRs.
  • To explore the mechanism of action of hallucinogenic drugs.
  • To highlight unresolved questions in GPCR pharmacology and drug action.

Main Methods:

  • Review of existing literature on GPCRs, agonist-trafficking, and hallucinogenic drug mechanisms.
  • Analysis of signaling pathways downstream of serotonin 5-HT2A receptors (5-HT2ARs).
  • Comparison of in vitro and in vivo effects of various psychoactive compounds.

Main Results:

  • Agonist-trafficking model explains differential signaling by distinct receptor conformations.
  • Hallucinogenic drugs (LSD, psilocybin, mescaline) activate 5-HT2ARs, inducing behavioral responses.
  • Non-hallucinogenic analogs (lisuride, ergotamine) show similar in vitro 5-HT2AR activity but do not induce similar states.

Conclusions:

  • Agonist-trafficking provides a framework for understanding biased GPCR signaling.
  • The differential effects of hallucinogens and non-hallucinogens highlight the complexity of 5-HT2AR pharmacology.
  • Further research is needed to fully elucidate the mechanisms underlying hallucinogenic drug action.