Current Medicinal Chemistry
March 1, 2009
Javier González-Maeso, Stuart C. Sealfon
74 citations
G protein-coupled receptors (GPCRs) are the most common target for therapeutic drugs. The traditional ternary complex model, where receptors shift between active and inactive states, has been revised because different agonists can activate distinct signaling pathways from the same receptor. This agonist-trafficking model proposes that agonists stabilize unique receptor conformations that preferentially trigger specific pathways. Hallucinogenic drugs like LSD, psilocybin, and mescaline, which act on serotonin 5-HT2A receptors, offer a useful system to study this phenomenon. Non-hallucinogenic chemicals like lisuride show similar in vitro activity at the same receptor but do not induce hallucinogenic effects, highlighting unresolved questions about how agonist-trafficking determines behavioral outcomes.
Current Medicinal Chemistry
October 1, 2002
M S Levi, R F Borne
70 citations
Ibogaine, a naturally occurring alkaloid, has been reported to interrupt cravings for alcohol, cocaine, and opiates. Other alkaloids from Tabernanthe iboga, such as ibogamine and tabernanthine, offer insights into structure-activity relationships at receptors involved in addiction. The synthetic congener 18-MC shows potential as an anti-addictive agent without ibogaine's hallucinogenic effects. Acamprosate, BP 897, GBR12909, lofexidine, and memantine have also shown promising results. Currently, no drugs are approved in the U.S. for treating addictions to cocaine, methamphetamine, other stimulants, or PCP.
Current Medicinal Chemistry
December 13, 2019
Genís Ona, José Carlos Bouso
15 citations
Developing highly selective drugs for central nervous system disorders has proven unsuccessful. Multi-target ligands, which act on multiple biological pathways, are now proposed as treatments offering better efficacy and safety. Natural products, including psychoactive drugs like ayahuasca and cannabis, exemplify this multi-target approach and show therapeutic promise for psychiatric and neurological conditions. This text describes how research on psychoactive drugs can be combined with polypharmacology, using ayahuasca and cannabis as examples, and discusses the advantages and disadvantages of this strategy.
Current Medicinal Chemistry
August 20, 2009
John S. Adams
7 citations
Pyramidal neurons in layer 5 of the cerebral cortex, crucial for learning and memory, have dendrites that can switch between long-term depression and potentiation based on summed inputs from many interneurons and distant neurons. Serotonin is a key neurotransmitter involved with these neurons and has been linked to psychosis, psychedelic states, and sacred dreams. This review discusses chemicals and receptors important for pyramidal neurons, including opioids, nicotine, scopolamine, psilocybin, LSD, mescaline, ergot alkaloids, salvinorin A, and ergine, which interact with opioid, nicotinic, muscarinic, and serotonergic receptors. It proposes that each receptor has a natural agonist and antagonist, often peptides, and suggests possible peptide structures for these, offering new avenues for exploring pyramidal neuron functions in health and pain management.
Current Medicinal Chemistry
June 2, 2025
Jinlong Zhang, Xingxing Dang, Jiang Lin et al.
A bibliometric analysis of 30 years of research on MDMA-assisted therapy for PTSD, anxiety, and depression shows a substantial increase in publications over the past decade. The United States leads in output, the Multidisciplinary Association for Psychedelic Studies (MAPS) is the most productive institution, and Rick Doblin is a highly influential researcher. The research focus has shifted from studying MDMA's neurotoxicity to exploring its therapeutic mechanisms, safety, and clinical applications. The analysis identifies key research trajectories and challenges, including the need for improved trial design, greater sample diversity, and evaluation of long-term effects to support clinical integration.
Current Medicinal Chemistry
April 28, 2026
Long-term memory remains stable for decades while supporting rapid, flexible cognition, a puzzle that synaptic plasticity alone does not fully explain given continuous protein turnover. The author hypothesizes that memory is encoded in stable, folded glycoprotein patterns within synaptic environments. This review examines how such persistent molecular architectures could enable dynamic information processing through quantum-enabled chemical mechanisms. Drawing on recent advances in glycobiology, enzymology, quantum biology, and medicinal chemistry, it proposes that proton and electron tunnelling offer a plausible, experimentally grounded mechanism for reading out stable glycoprotein-encoded information without requiring large-scale molecular rearrangement or long-lived macroscopic quantum coherence. This approach reconciles molecular stability with cognitive flexibility and yields testable predictions relevant to neurodegenerative disease and drug discovery.
Current Medicinal Chemistry
September 24, 2025
Memory could be encoded as patterns of hydrogen-bonded 'frozen' conformers of neuronal glycoproteins, leveraging the many asymmetric centers in sugar molecules for stable information storage. This mechanism may underlie learning, storage, and recall. Penrose and Hameroff's orchestrated objective reduction (Orch OR) theory proposes quantum superpositions and entanglement in neuronal microtubules produce conscious awareness. Recent work by Babcock et al. (2024) demonstrated ultraviolet super radiance in tryptophan-containing protein networks, including tubulin, under physiological conditions, suggesting protein architectures can support collective excitonic states. A unified model proposes microtubules as quantum information processors routing distributed information, while glycoprotein conformational patterns serve as a molecular memory register, bridging quantum events and cognitive function.