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It we all experience changes in mood sometimes we feel happy and energetic usually don’t last long and we can go about our normal daily routine however unusually long periods of sadness guilt is what we call depression sometimes depression can occur alone and other with bipolar disorder experience periods of depression alternating with energetic now treatment of depression and
Bipolar disorder often involves use neurotransmitters in the brain this led to development of monoamine hypothesis three key monoamines namely serotonin norepinephrine and dopamine another postsynaptic receptors to upregulate thus leading to depression an abnormal functioning gene that is responsible for causing depression now and they don’t accurately explain everything that
We observed in research work so now let’s switch gears and let’s their mechanism of action antidepressants can be divided into five short number two serotonin norepinephrine reuptake inhibitors snris for short number four monoamine oxidase inhibitors maois for short and lastly number five draw some neurons that will help us understand how these antidepressants in other words
Serotonin producing neuron and next to it i’m going to draw neuron now these two neurons interact with their postsynaptic counterparts so neuron are beta and alpha-1 while postsynaptic receptors of serotonergic keep in mind that there’s quite a few subtypes of serotonin receptors but for synthesized from an amino acid tryptophan by serotonergic neurons and side norepinephrine
Is synthesized from an amino acid tyrosine by noradrenergic neurons and it is also stored there in vesicles awaiting release so now what exactly happens when these neurotransmitters are released well there are released they begin to stimulate the receptors and at the same time they’re norepinephrine is reabsorbed by norepinephrine transporter abbreviated norepinephrine get
Reabsorbed back to their neurons they’re partially metabolites by an enzyme monoamine oxidase abbreviated mao now let’s move reuptake inhibitors so as you can tell from their name serotonin transporter this results in increased levels of serotonin available escitalopram fluoxetine fluvoxamine paroxetine and sertraline now besides such as generalized anxiety post-traumatic
Stress disorder and pretty straightforward but then you may wonder why these antidepressants take into why this happens so recently scientists discovered that in people stuck on these rafts g-proteins lack access to molecule called cyclic amp was discovered that ssris also tend to build up in these lipid rafts which resulted in the gradual movement of g-proteins out of the
Rafts toward regions maximum benefit now when it comes to side effects excessive stimulation of irritability next excessive stimulation of spinal serotonin receptors may lead serotonin receptors in the gastrointestinal tract as well as in the synaptic serotonin which in turn may lead to unpleasant symptoms such as serotonin norepinephrine reuptake inhibitors so snris just
Like ssris but what makes them different is their ability to additionally inhibit and norepinephrine which can then bind to the postsynaptic receptors examples of snris include venlafaxine desvenlafaxine duloxetine and levomilnacipran snris have been shown to be also effective in reducing pain associated fibromyalgia as well as other pain caused by neuropathy this unique
Pharmacological noradrenergic activity within the central nervous system now when it comes additional noradrenergic activity snris may increase blood pressure core chemical structure which contains three rings connected together unlike straight forward so just like snris tcas were found to primarily agents do this with different level of selectivity in other words some tcas
Such then serotonin transporter furthermore tcas also block many other receptors such however blockade of these other receptors is thought to be responsible include amitriptyline amoxapine clomipramine desipramine doxepin imipramine action they also proved to be beneficial in treatment of other medical problems for example amitriptyline and nortriptyline have been used for
Migraine such as doxepin have been used for insomnia now when it comes to side dizziness inhibition of histamine receptors leads to sedation and blurred vision dry mouth constipation and urinary retention effects similar to antiarrhythmic agents such as quinidine this ultimately can inhibitors so monoamine oxidase is a mitochondrial enzyme that degrades subtypes a and b
Which are differently distributed in tissues such as brain gut serotonin but will also metabolize norepinephrine and dopamine while mao mao subtype a is thought to be responsible for antidepressant effects straightforward maois inhibit the activity of mao enzymes preventing now examples of maois include isocarboxazid phenelzine and tranylcypromine subtype b which in turn
Makes them effective for treatment of depression which is a selective inhibitor of mao subtype b and therefore has been shown results from depletion of dopamine so now on the surface it seems like maois in practice there are usually a very last choice and the reason is that maois show not only high incidence of drug-drug interactions but also drug-food they play important
Role in breakdown of monoamines ingested in food the is contained in foods that have been aged or fermented now built-up tyramine catecholamine releasing agent the release of large amount of stroke this is why patients that are prescribed maois due to lack of other we can move on to atypical antidepressants this class includes fit into the other classes examples of atypical
Antidepressants now each of these drugs has a little different mechanism of action so being used for depression bupropion was found to be effective in reducing alpha-2 receptors mirtazapine increases noradrenergic and serotonergic have some postsynaptic serotonin receptor blocking activity as well as trazodone and nefazodone their therapeutic effect is thought to be
Postsynaptic serotonin receptors of subtype 2a which are the bad contribute to depression additionally both of these agents antagonize histaminic h1 and adrenergic alpha-1 receptors which may account for their sedative effects next we have vilazodone which has similar sounding name to so vilazodone is a serotonin partial agonist reuptake inhibitor meaning it finally we
Have vortioxetine which has a mechanism of action that is still a serotonin reuptake as well as activate and block different subtypes of serotonin briefly discuss lithium which is a mood stabilizing drug in its own class but currently for bipolar disorders unfortunately lithium has a fairly levels can lead to toxicity now despite years of research the exact mechanism of
Few mechanisms of action have been proposed one in particular that has been extensively studied states that lithium inhibits the recycling of bear with me so in the inositol lipid pathway g-protein coupled receptors such cleaves phosphatidylinositol 4,5-bisphosphate pip2 for short for short and inositol 1,4,5-trisphosphate ip3 for short next ip2 for short and at this point
The enzyme inositol phosphatase and lastly another inositol phosphatase dephosphorylates ip1 to does is it inhibits both inositol phosphatase enzymes and thus decreases system now lithium also was found to inhibit glycogen-synthase-kinase-3 we have this wnt proteins which are secreted glycoproteins acting as a family they induce certain reactions which ultimately result
In inhibition of synapse formation plasticity and neurogenesis what the research has found several neurological and psychiatric disorders such as bipolar disorder so particular mechanism contributes to its therapeutic effect unfortunately this neurotransmitter systems in the brain and i think at this point you had enough i hope you enjoyed this video and as always stay tuned for more
Transcribed from video
Pharmacology – ANTIDEPRESSANTS – SSRIs, SNRIs, TCAs, MAOIs, Lithium ( MADE EASY) By Speed Pharmacology
