NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). (S)-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, (R)-ketamine...
Deficiencies in standard of care antidepressants are driving novel drug discovery. A new age of antidepressant medications has emerged with the introduction of rapid-acting antidepressants with efficacy in treatment-resistant patients. The newly approved medicines and those in clinical development for major depressive disorder (MDD) are documented in this scoping review of newly approved and...
INTRODUCTION: Major depressive disorder remains a prevalent world-wide health problem. Currently available antidepressant medications take weeks of dosing, do not produce antidepressant response in all patients, and have undesirable ancillary effects. AREAS COVERED: The present opinion piece focuses on the major inroads to the creation of new antidepressants. These include N-methyl-D-aspartate...
Interest in developing minimal side-effect NMDA receptor antagonists for neurological and psychiatric disorders has been energized by the recent introduction of esketamine into clinical practice for treatment-resistant depression. Structural analogs of dextromethorphan bind with low affinity to the NMDA receptor ion channel, have functional effects in vivo, and generally display a lower...
Substance abuse disorder continues to have devastating consequences for individuals and society and current therapies are not sufficient to provide the magnitude of medical impact required. Although some evidence suggests the use of ketamine in treating various substance use related- symptoms, its adverse event profile including dissociation, dysphoria, and abuse liability limit its potential...
Conventional antidepressants (biogenic amine mechanisms) are not fully efficacious (e.g., symptoms remain after treatment, not all patients respond), produce effects only after weeks of daily dosing, and do not impact all disease symptoms. In contrast, a new class of antidepressants has been emerging since 2006 that has demonstrated rapid onset, large effect size, activity after only a single...
Background: Conventional antidepressants are thought to produce their impact on clinical symptoms by increasing the central availability of biogenic amine neurotransmitters (the monoamine hypothesis of depression). These drugs continue to be the primary medicines used in major depressive disorder. Although they have biological effects after acute dosing, full antidepressant response generally...
Both anecdotal reports in humans and preclinical studies indicate that ibogaine interrupts addiction to a variety of abused substances including alcohol, opiates, nicotine and stimulants. Based on the similarity of these therapeutic claims to recent preclinical studies demonstrating that N-methyl-D-aspartate (NMDA) antagonists attenuate addiction-related phenomena, we examined the NMDA...