The mechanisms of action of anti-depressants, neuroleptics and anti-manic drugs

Health outcomes are better influenced by a variety of substances of internal or external origin. Nevertheless, the outcomes are often aggravated by certain potential effects of substances acting on them. In fact, the substances are nothing but the drugs or medication prescribed by physian or a doctor.

These medications show action on various organ systems of the body to alleviate the pain and inflammation or any abnormal condition which disturb the routine hygiene. The factors contributing to the action of drug on a specific organ or organ system of body are interlinked to the route of administration and dosage. However, mechanism of action do plays role in influencing the action of medication.

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Especially, medications that exert action on central nervous system (CNS) are very important as they reflect the psychological, behavioral and mood patterns in individuals.There are a spectrum of CNS disorders that pose a threat to the neuropsychological functioning. To overcome this aberration, a variety of CNS drugs have been introduced into the pharmacopeia. These include anti-depressants, neuroleptics and anti-manic drugs. There is a need to know the mechanism of action of drugs related to this special category of CNS drugs.

Antidepressants are a class of medicines which cure depression. They are mostly prescribed for patients who have alterations in concentration, appetite, sleep and mood.The recovery from such conditions involves few weeks. There are various types of antidepressant drugs. The mechanism of antidepressant drugs is connected to monoamine hypothesis.

This is because depression occurs due to lack of biogenic monoamines like dopamine, DA, noradrenaline, NA, serotonin, 5-HT. Antidepressant drugs are thus categorized with regard to their potential to enhance monoaminergic transmission. Studies related to microdialysis, electrophysiological and behavioural studies have shown that serotonin (5-HT) receptors, mainly 5-HT1A, 5-HT1B and 5-HT2C sub-types, play vital role in their antidepressive mode of action.

Here, antidepressants activate neurotransmitter which occurs through a rise in synaptic endogenous serotonin levels at specific locations of brain. This results in several G protein stimulation which are linked to neurotrophic factors like brain-derived neurotrophic factor (BDNF), transcription factors, signal transducing receptors. Hence, it is the transduction mechanism underlying depression (Bourin et al., 2002).

The treatment strategies focused on Depressive disorders have achieved remarkable outcome with serotonin noradrenaline reuptake inhibitors: SNRI and selective serotonin reuptake inhibitors: SSRI (Bourin et al., 2002). For treating, major depressive disorder (MDD),The novel class of drugs such as SSRI, SNRI and norepinephrine-dopamine reuptake inhibitor were identified as first-line” therapies.

They have better withstanding potential and safety compared to older medications tricyclic antidepressants (Koenig &Thase, 2009). According to latest update, there is an increasing trend in the use of antidepressant medication over a period of 1996 to 2005 (Olfson & Marcus, 2009).

Next, the other categories of drugs are Neuroleptics. These are medications prescribed for treating psychosis and mainly work by inhibiting dopamine D2-like receptors

(Treatment of Pediatric Movement, 2011). Therefore, the mechanism of neuroleptics is the main CNS dopamine network which begins in the substantia nigra of brain and extends till the regions of caudate, putamen, and corpus striatum.This action makes it contribute to extrapyramidal side effects like tardive dyskinesia and Parkinsonism.In another mechanism the dopamine pathway extends to the nucleus accumbens, amygdala, cingulate gyrus which are known as limbic regions that control emotions.

A Neuroleptic drug suppressing this pathway causes anti-psychotic effects.Subsequent pathway begins in the hypothalamic region of brain and extends to the region of anterior pituitary. Inhibition of this particular pathway by neuroleptic medications results in rise in prolactin levels causing amenorrhea and sexual dysfunction (Neuroleptic Pharmacology,n.d.).

Several hypotheses have been put forward to better explain the mechanism of neuroleptic drugs. In one hypothesis, it was described that in vivo, D2 blocking agents retard the firing process of dopamine neurons thus leading to a reduction in release of dopamine in the striatum.

This causes the D1 receptors become unload of transmitters. In experiments conducted on anaesthetized an free moving rats, D2 antagonists enabled a rise in firing proportion of dopamine neurons. Recently, another explanation was proposed which emphasizes on the interfering stages between D2 blockade and antipsychotic effects (Miller, 2009).

Present in the striatum at a low proportion, are a category of neurons known as “large cholinergic interneurones. Their function is release of acetyl choline (ACh) which is regulated by dopamine, that blocks these neurons at receptors of D2.Thus, agents that serve as D2 blockers contribute to rise in firing rate, and Ach release by cholinergic interneurones. For the actions to occur at cellular level, there is need of another receptors namely, muscarinic receptors.

There are five such receptors where Ach is supposed to exert its effect. M1, M2, M4 are located in the striatum.An animal lacking M2 receptor dose not produce tremors following cholinergic agonist administration, indicating its significance for that function(Miller,2009). The tremor behavior effect is due to lessened striatal ACh release instead of lack of this receptor type induced postsynaptic effect.

M1 receptor is present on medium spiny neurons and blocks potassium current causing a rise in the excitability of neurons. Hence, D2-blocking agent generated motor side effects are facilitated via rise in cholinergic stimulation of M1 receptors.M4 receptor likely reduces the synthesis of cyclic adenosine monophosphate (cAMP) synthesis, and when this receptor is stimulated, the synthesis of cAMP ,activated through other ways is reduced.

Thus, M1receptor activation leads to extrapyramidal side effects (EPS) and M4 receptor activation leas to reduced cAMP synthesis. On the whole, the antipsychotic drugs action is to lessen the cAMP formation through the routes of D2 blockade and increased firing in cholinergic neurons (Miller, 2009).The current trends in prescription of neuroleptics indicate that since the year 2000, there was an increase due to rise in the prescription of second-generation antipsychotics (SGAP).

This has drawn increasing attention on children and adolescents with regard to the increasing exposure to neuroleptics by general population and also to evaluate the SGAP’s risk and benefit index for disorders not relevant to psychosis (Verdoux,Tournier,&Begaud,2010).The final class of drugs to be discussed in this part of description is antimanic drugs. These are used for the treatment of mania or bipolar disorders associated with other disorders that are affective in nature (Medical Dictionary Online,2008).

There are various antimanic drugs the most common being the Lithium carbonate, carbamazepine and valproate semisoium. Some of the various forms mechanisms underlying the therapeutic effects of the drug Lithium carbonate, are, it causes reduced sensitivity of neurotransmitter postsynaptic receptor; induces activation of Na+ exit from cells when there is an elevation in the intracellular Na+ ,as observed in depression. This process is based on the Na+/K+pump mechanism stimulation.

This drug activates Na+ entry into cells when Na+ level is reduced intracellulalry as observed in manic conditions. It contributes to transfer of Na+ and Ca2+ ions Ca2+-dependent release of neurotransmitter, across cell membranes .This drug prevents both inositol phosphate `second messenger’ systems and cyclic AMP in the membrane .

This action facilitates the prolonged aside effects of hypothyroidism and nephrogenic diabetes insipidus by inhibiting TSH-sensitive adenyl cyclase and ADH-sensitive adenyl cyclase.Finally, it promotes for Mg2+ and Ca2 interaction leading to permeability of cell membrane at an increase level. Next, carbamzepine is another antimanic drug whose structure is equal to tricyclic antidepressant imipramine but has no known effect on the reuptake of monoamine reuptake.

It facilitates its mechanism by the blocking of limbic system’skindling phenomena.Finally, sodium valproate is another anti-manic drug. It exerts its therapeutic mechanism by retarding the breakdown process of GABA(?-amino butyric acid) by blocking semialdehyde dehydrogenase thus indicating a biochemical alteration of GABA defect .

This drug was believed to cross the blood brain barrier with sodium valproate which leads to the brain accumulation of valproate in increased concentration with equal dose of sodium valproate and valproate semisodium (Antimanic Drugs,n.d.). According to the available information, trends in the use of antimanic drugshas indicated a fall in the social rates in several countries in the recent period. This is due to an increased prescription of antimanic drugs which reflected a precise diagnostic oriented recommendation of drugs.

This trend also occurred with the use of selective serotonin reuptake inhibitors (SSRIs), antipsychotics (Shah & Lodhi, 2005). Therefore, all the classes of drugs mentioned above have a significant therapeutic effect on the CNS. There is a further need to explore the novel pathways that imply a faster treatment strategy with minimum side effects.

References

Antimanic Drugs: Radcliffe Publishing Oxford. (n.d.). Retrieved from www.radcliffe-oxford.com/books/…/1874/ch4-336859c0rdz.pdf

Bourin, M., David, D.J., Jolliet, P., & Gardier, A. (2002). Mechanism of action of antidepressants and therapeutic perspectives. Therapie, 57 (4): 385-96.

Koenig, A.M., &Thase, M.E.(2009).First-line pharmacotherapies for depression – what is the best choice? Pol Arch Med Wewn,119 (7-8): 478-86.

Medical Dictionary Online: What is Antimanic Drugs? (2008). Retrieved from http://www.medicaldictionaryonline.info/medical-term/Antimanic+Drugs

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): 302-314.

Neuroleptic Pharmacology. (n.d.) Retrieved from www.raymondcheong.com/…/DB49%20-%20Neuroleptic%20Pharm…

Olfson, M., & Mark, S. C. (2009). National Patterns in Antidepressant Medication Treatment. Arch Gen Psychiatry,66 (8): 848-85.

Shah. A., & Lodhi, L. (2005).The impact of trends in psychotropic prescribing on the method of suicide in the elderly. Med Sci Law,45 (2):115-20.

Treatment of Pediatric Movement Disorders. (2011). Retrieved from http://www.wemove.org/pediatric_treatment/medication_neuroleptics.html

Verdoux, H. Tournier, M., & Begaud, B.(2010).Antipsychotic prescribing trends: a review of pharmaco-epidemiological studies. Acta Psychiatrica Scandinavica,121, (1): 4-10.