Impairment in mitochondrial biogenesis and function plays a key role in depression and anxiety, both of which being associated with changes in fatty acid and phospholipid metabolism. The antidepressant effects of (R,S)-ketamine have been linked to its conversion into (2S,6S;2R,6R)-hydroxynorketamine (HNK); however, the connection between structure and stereochemistry of ketamine and HNK in the...
Post-traumatic stress disorder (PTSD) is a chronic and debilitating condition that is often refractory to standard frontline antidepressant therapy. A promising new approach to PTSD therapy is administration of a single sub-anesthetic dose of (R,S)-ketamine (Ket). The treatment produces rapid and significant therapeutic response, which lasts for only 4-7 days. In one of our studies, the mean...
Background and objectives: Trauma memories lay at the core in etiopathogenesis of post-traumatic stress disorder (PTSD). Using pharmacological and cognitive behavioral treatments that specifically target trauma memories can improve the outcome. Ketamine has been shown to rapidly improve symptoms in PTSD and comorbid depression, but unfortunately these effects are short-lived. Trauma...
Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-d-aspartate...
(R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism. The aim of the study was to examine the relationship between...
(R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non-targeted determination of...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • (R,S)‐ketamine is a phencyclidine derivative that was initially developed as an anaesthetic agent and which is currently being studied in the treatment of pain and depression. After administration, the drug is extensively N‐demethylated to (R,S)‐norketamine. The pharmacokinetics of ketamine and norketamine have been extensively studied in volunteers...
The interaction of ibogaine and phencyclidine (PCP) with human (h) alpha3beta4-nicotinic acetylcholine receptors (AChRs) in different conformational states was determined by functional and structural approaches including, radioligand binding assays, Ca2+ influx detections, and thermodynamic and kinetics measurements. The results established that (a) ibogaine inhibits (+/-)-epibatidine-induced...
The interaction of 18-methoxycoronaridine (18-MC) with nicotinic acetylcholine receptors (AChRs) was compared with that for ibogaine and phencyclidine (PCP). The results established that 18-MC: (a) is more potent than ibogaine and PCP inhibiting (+/-)-epibatidine-induced AChR Ca(2+) influx. The potency of 18-MC is increased after longer pre-incubation periods, which is in agreement with the...
PURPOSE: Characterization of the binding sites for ibogaine analogs on the nicotinic acetylcholine receptor (AChR) in the resting and desensitized states. METHODS: [ 3 H]18‐methoxycoronaridine ([ 3 H]18‐MC) Scatchard‐plots using Torpedo AChR membranes, [ 3 H]TCP (a well characterized noncompetitive antagonist) competition binding experiments and Schild‐type analysis, analog‐induced binding...
The enantioselectivity of the interaction of dextromethorphan (DM) and levomethorphan (LM) with an immobilized alpha 3 beta 4 subtype of the nicotinic acetylcholine receptor (nAChR) liquid chromatographic stationary phase has been compared to DM- and LM-induced non-competitive blockade of nicotine-stimulated 86Rb(+) efflux from cells expressing the alpha 3 beta 4-nAChR. The association rate...