Current Medicinal Chemistry
March 1, 2009
Javier Gonzalez-Maeso, Stuart 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
December 13, 2019
Genís Oña, 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.