A systems and control theoretic approach to dynamic neurotransmitter balance: Normal, abnormal, and “catastrophic”

Abstract We formulated a pharmacological–physiological systems analysis and control theory based on interactive neuronal feedback loops (the effects of endogenous neurochemical diseases and exogenous psychotropic and other CNS drugs on neurotransmitter synthesis and release, reuptake, and metabolism) for normal, abnormal, and catastrophic situations. We were concerned primarily with the problems of stability or instability which might lead the system to exhibit catastrophic behavior. We set up the systems diagrams for the neurotransmitter systems and in that single framework were able to describe endogenous neurochemical disorders, the effect their drug treatment modalities had on the dynamic neurochemical balance, the effect psychotropic or other CNS drugs such as narcotics and narcotic antagonists had on neurotransmitter balance, and the interactive effect that multiple drug administration would have on neurotransmitter balance. Endogenous neurochemical disorders such as schizophrenia, Parkinsonism, depression, and mania should show up mathematically either as overly damped solutions if there is too little normal neurotransmitter or as catastrophically divergent instabilities if there is too much normal neurotransmitter. Improper mixed drug therapies, as well as the devastating effect of eating foods such as cheese (which contains sympathomimetic amines which potentiate the release of catecholamines from the presynaptic nerve endings) while on MAOI therapy also show up as mathematical, usually catastrophic, instabilities. We also indicated how this systems analysis and control theory could be put on small interactive computer terminals for use in clinical management and proper drug therapy of patients with neurochemical disorders.