Dysregulation of glutamatergic neurotransmissionhas been widely postulated as being involved in the etiology of schizophrenia. In the etiology of schizophrenia I have been stressing the dysregulation tricarboxylic acid (TCA) cycle via dysregulation of aconitase and the 2-oxoglutarate dehydrogenase complex stemming from shortages of coenzyme A.
The TCA cycleproduces 2-oxouglutarate. .L-glutamatecan be synthesized from 2-oxoglutarate. With dysregulation of the TCA cycle there can be a disruption in the synthesis of L-glutamate which would adversely affect glutamatergic neurotransmission whereby symptoms of schizophrenia could develop. .
Increasing glutamatergic neurotransmission alone via glutamate receptor agonists, however, does not solve the problem. The TCA cycle is still dysregulated.
There is strong focus on NMDAglutamate receptors in research on schizophrenia. Dysregulation of the TCA cycle, however, would dysregulate glutamatergic neurotransmission generally and also dysregulate GABA neurotransmission as GABA is synthesized from L-glutamate . D-serine which is an NMDA receptor agonist has failed in phase II trials where d-serinewas being tested for effectiveness against symptoms of schizophrenia though a deuterated (i.e patenable) form of D-serine could still be effective for hair loss.
I hold that only addressing NMDA receptors will always fail in terms of the treatment of schizophrenia. Dysregulation of glutamatergic neurotransmission plays a key role in the etiology of schizophrenia, however, to address dysregulations of glutamatergic neurotransmission in schizophrenia dysregulation of the TCA cycle must be first addressed.
Ketamine is being used in the treatment of major depressive disorder. Ketamine is a glutamate NMDA receptor antagonist. A ‘modulating ‘effect of ketamine on NMDA receptors has been stated as giving rise an antidepressant effect of ketamine in major depressive disorder.
Glutamate toxicity due to calcium influx through L-, P/Q-, N-type voltage-gated calcium channels and NMDA receptor calcium channels is inhibited by taurine with taurine having a neuroprotective effect. The treatment presented on the Bipolar Depression page, which includes taurine, would address glutamatergic neurotransmission and could be effective for major depressive disorder.
Addressingglutamatergic neurotransmission via taurine is much preferable to addressing glutamatergic neurotransmission via ketamine. Research points to supplemental taurine as reducing homocysteine levels (Ahn, 2009), reducing cholesterol levels in animals (Guo et al., 2017; Chen et al., 2012) having an anti-obesityeffect, as being negatively associated with ischemic heart disease, as ameliorating diabetes and points to taurine deficiencies as resulting in premature aging. Research on rats points to the neurotoxic effects of repeated ketamine exposure as being due to changes in purine metabolism and glycerophospholipid metabolism in the prefrontal cortex that persist even after ketamine withdrawal.
Acamprosateis used to assist with alcohol abstinence. Acamprosate is compound that is structurally very closely related to taurine. Would taurine be as effective for alcohol abstinence as acamprosate? Sometimes small changes in molecular structure can have large effects on the actions of drugs. Acamprosate could have advantages over taurine for alcohol dependence but then again maybe the advantage of acamprosate was that at one time acamprosate was patentable.