5.1. PRINCIPLES
OF PHARMACOLOGICAL
REGULATION OF CNS FUNCTIONS
Nearly all medicinal substances that affect the central nervous system directly or indirectly change the synaptic transmission. Their action can be preor postsynaptic. Drugs influence the synthesis, accumulation, metabolism or release of the neurotransmitter. Thus, Levodopa, being a dopamine precursor, increases the synthesis of the latter in the CNS (fig. 5.1, а). Antiepileptic drug Tiagabine inhibits the enzyme GABA transferase that breaks down GABA (gamma-am-inobutyric acid) (fig. 5.1, b). Sympatholytics decrease accumulation of noradrenaline in the vesicles of presynaptic endings, which results in enzymatic breakdown of the cytoplasm noradrenaline outside of the synaptic vesicles (fig. 5.1, c). Amphetamine and CNS stimulators increase monoamine release from the presyn-aptic endings (fig. 5.1, d). A neurotransmitter released into the synaptic cleft undergoes neuronal reuptake or is broken down by the enzymes. Tricyclic antidepressants block reuptake of monoamines by the presynaptic endings (fig. 5.1, e). Antiparkinsonian drug Entacapone inhibits the enzyme catechol-O-methyltransfer-ase, dopamine-destroying enzyme (fig. 5.1, f).
Neurotransmitters released into the synap-tic cleft are agonists of postsynaptic receptors whose activation leads to neuronal activation or inhibition (fig. 5.1, g). Most CNS neurons (over 80%) are sensitive to amino acid neuro-transmitters. These substances enable transmission of most sensory, motor and other signals over the neural network. Excitatory neuro-transmitters include glutamate which ensures quick synaptic transmission. Glutamate released into the synaptic cleft through Са2+-dependent exocytosis activates three types of ionotropic glutamate receptors: AMPA, kainate and NMDA receptors. АМРА receptors are located on nearly all CNS neurons. Activated AMPA receptors allow Na ions to enter the neurons, ensuring fast depolarization. Kainate receptors are also widely common in the CNS (especially in the hippocampus and cerebellum) and ensure fast depolarization of neurons due to the entry of sodium ions and exit of potassium ions. Stimulation of kainate and AMPA receptors causes fast depo-