Long-term memory exhibits a remarkable problem: it is extraordinarily stable over decades, yet it supports rapid, flexible cognition, logic, and conscious awareness. Classical neuroscience has largely attributed memory to synaptic plasticity and networklevel dynamics; however, these mechanisms alone do not adequately explain the molecular durability of memory traces in the face of continuous...
The author had previously proposed that memory could be encoded as patterns of hydrogen-bonded "frozen" conformers of neuronal glycoproteins. These stabilised molecular patterns represent an ideal template for information storage in the human brain because of the large number of asymmetric centres present in sugar molecules with attached hydroxyl groups. Hydrogen bonding of hydroxyl groups...
The incidence of psychiatric disorders, such as post-traumatic stress disorder (PTSD), anxiety, and depression, has been steadily increasing, while current treatment approaches remain limited in efficacy. As a result, there is an urgent need to explore more effective therapeutic interventions. In recent years, MDMA (3,4- methylenedioxymethamphetamine)-assisted therapy (MDMA-AT) has emerged as a...
In the drug development, the formation of highly selective ligands has been unsuccessful in the treatment of central nervous system disorders. Multi-target ligands, from the polypharmacology paradigm, are being proposed as treatments for these complex disorders, since they offer enhanced efficacy and a strong safety profile. Natural products are the best examples of multi-target compounds, so...
At central synapses, glutamate is the main excitatory neurotransmitter. Once released from presynaptic terminals, glutamate activates a number of different glutamatergic receptors one of which is the ligand gated ionophore glutamatergic subtype N-methyl-D-aspartate receptors (NMDARs). NMDARs play a crucial role in controlling various determinants of synaptic function. N-acetylaspartylglutamate...
Pyramidal neurons in layer 5 of the cerebral cortex are involved in learning and memory and have complex connections with other neurons through a very large array of dendrites. These dendrites can switch between long term depression and long term potentiation depending on global summation of various inputs. The plasticity of the input into pyramidal neurons makes the neuronal output variable....
Seven transmembrane domain receptors, also termed G protein-coupled receptors (GPCRs), represent the most common molecular target for therapeutic drugs. The generally accepted pharmacological model for GPCR activation is the ternary complex model, in which GPCRs exist in a dynamic equilibrium between the active and inactive conformational states. However, the demonstration that different...
Chemical substance abuse has tormented mankind throughout history. A number of chemical approaches have been employed in an attempt to treat chemical addiction. Unfortunately, most of these have proven unsuccessful though several chemical entities have been shown to be moderately effective. The naturally occurring alkaloid ibogaine has been reported to interrupt the cravings for alcohol,...