How Therapeutic Drugs Alter Neurotransmission at Synapses

This essay explores the mechanisms by which therapeutic drugs, used to treat neurological and psychiatric disorders, alter neurotransmission at synapses. It focuses on the dopaminergic, serotonergic, and noradrenergic systems, which are frequently targeted by drugs due to their central role in regulating cognitive and motor functions. The discussion covers both presynaptic and postsynaptic approaches. Presynaptic mechanisms involve altering neurotransmitter levels in the synaptic cleft, such as through monoamine oxidase B inhibitors or drugs that reduce vesicular-mediated release. Postsynaptic mechanisms involve direct action on postsynaptic receptors, with examples including agonists and antagonists. The essay also explains how receptors can be activated, partially activated, inactivated, or blocked by drugs. References to key research papers support the explanation of these mechanisms.

Explanation of the mechanisms
by which therapeutic drugs used
to treat neurological or psychiatric
disorders can alter
neurotransmission at synapses
Introduction
Even though a broad range of symptoms are found for different neurological and psychiatric
disorders, but dopaminergic, serotonergic, and noradrenergic systems, are frequently targeted by
the drugs. These are chiefly used in the therapeutic management of the neuropsychiatric
disorders because the neurotransmitter systems contribute centrally in the regulation of a vast
array of cognitive and motor functions (Kanwar, et al., 2012).

Discussion
In recent times, the biogenic amine neurotransmitter systems, specifically the dopaminergic,
serotonergic, and noradrenergic receptors, transporters, and metabolic enzymes, encompass the
major neurological and psychiatric drug targets (Molinoff, 2018). It is because the biogenic
amine systems are fundamental modulators of neuronal excitability, and the molecular elements
of these systems are present at chemical synapses, which are sites that are available for drug
intervention. The therapeutic treatment of neurological and psychiatric disorders is mainly
dependent upon the variation of the central nervous system (CNS) neurotransmission with the
drugs that mediate at the synapses (Sharifi, 2013). The excitability of the neuron is modulated
using primarily two therapeutic at synapses which are presynaptic and postsynaptic. In the
presynaptic approach the neurotransmitter levels is altered in the synaptic cleft. It occurs when
the quantity of endogenous neurotransmitter changes for circulating into the synaptic cleft.
Presynaptic approach is also achieved by changing the quantity of neurotransmitter which is
reuptaken into the presynaptic terminal. Dopaminergic synapse is an example of these
approaches as shown in Fig. 1. Like, the monoamine oxidase B inhibitors, such as selegiline,
block dopamine degradation that increases the availability of the block dopamine for release and
the inhibitors of block dopamine synthesis, like α-methylparatyrosine, decrease the availability
of block dopamine for release. Drugs such as tetrabenazine reduce the vesicular-mediated release
by obstructing the vesicular monoamine transporters, which stops the storing of neurotransmitter
into vesicles (Wimalasena, 2011). In the postsynaptic approach, the level of endogenous
neurotransmitter is altered directly on the postsynaptic receptors. In this approach, the chemical
agents act directly at this point. Like agonists, such as block dopamine or the antiparkinsonian
drug pergolide, stimulates the block dopamine receptors directly, while the neuroleptic drugs

such as thioridazine and haloperidol obstruct the activation of block dopamine receptor (Miller,
2009).
Fig. 1
A receptor may act in four different ways when the drug binds to the primary site reversibly.
Receptor may get activated, partially activated, inactivated, or becomes unable to be activated.
The agonists completely activates receptors, partial agonist activates the receptors partially,
inverse agonist inactivates the receptors and the antagonist stops receptors from getting
activated. Like, the block dopamine is an agonist of block dopamine receptors, bromocriptine
used in Parkinson’s disease is a partial agonist at D2 receptors. In the thermodynamic process
called, the agonist binding causes a conformational alteration in the receptor and transforms it
from the inactivated state to the activated state. The neutral antagonist binding is
characteristically indifferent to the conformational state of its receptor, as it must only lodge at
the primary site instead of lodging and then inducing an alteration in it.

Conclusion
Various mechanisms are used to treat neurological or psychiatric disorders through which the
therapeutic drugs alter neurotransmission at synapses such as pre-synaptic and post-synaptic
alterations.
References
Kanwar, J. R., Sriramoju, B. & Kanwar, R. K., 2012. Neurological disorders and therapeutics
targeted to surmount the blood–brain barrier. Int J Nanomedicine, Volume 7, p. 3259–3278.
Miller, R., 2009. Mechanisms of Action of Antipsychotic Drugs of Different Classes,
Refractoriness to Therapeutic Effects of Classical Neuroleptics, and Individual Variation in
Sensitivity to their Actions: PART I. Curr Neuropharmacol, 7(4), p. 302–314.
Molinoff, P. B., 2018. Neurotransmission and the Central Nervous System. In: Goodman &
Gilman's: The Pharmacological Basis of Therapeutics. 13 ed. s.l.:McGraw Hill.
Sharifi, M. S., 2013. Treatment of Neurological and Psychiatric Disorders with Deep Brain
Stimulation; Raising Hopes and Future Challenges. Basic Clin Neurosci, 4(3), pp. 266-70.
Wimalasena, K., 2011. Vesicular Monoamine Transporters: Structure-Function, Pharmacology,
and Medicinal Chemistry. Med Res Rev, 31(4), p. 483–519.