February 1, 2023

Serotonin-noradrenaline reuptake inhibitors (SNRIs) are medications that are evidence-based in the treatment of depression, anxiety, panic disorder and some other mood disorders.

Welcome to hub bytes i’m senile reggae consultant psychiatrist from cycling today i’ll be taking you through the mechanism of action of snri snri stands for serotonin nor adrenaline reuptake inhibitor nor adrenaline is also known as norepinephrine in the prefrontal cortex which is postulated to be involved in the pathogenesis of depression there are three key

Neurotransmitters noradrenaline serotonin and dopamine what we do know is that from the presynaptic neuron the neurotransmitter is released it accumulates in the synaptic cleft and then binds to the receptors in the postsynaptic neuron resulting in activation and exerts its effect finally what we do know is there are proteins known as transporter proteins that

Take up these neurotransmitters back into the presynaptic neurons where they’re broken down narrow adrenaline is broken down by nat which is the nor adrenaline transporter serotonin is the cert protein which is serotonin transporter and dopamine is by dat but you can see here that is missing and why is that because in the prefrontal cortex that is missing and

The work of that is done by nat so the nor adrenaline transporter is essentially the protein is the transporter protein that will take up the dopamine into the presynaptic neuron dopamine as we know is also broken up down by other enzymes such as comms what happens when we administer a snri we know that an snri is a reuptake inhibitor so it blocks the reuptake

Of noradrenaline of serotonin and the way it does that is by blocking the transporter proteins so by blocking the cert the serotonin transporter protein there is accumulation of serotonin in the synaptic cleft allowing for action by blocking nat which is a noradrenaline transporter there is accumulation noradrenaline allowing for the action the question is how

Does an snri increase dopamine as well what happens is it can be considered as a dual agent where serotonin and noradrenaline are both increase in the synaptic cleft but what happens is the when the dopamine is released from the presynaptic neuron some of it will be broken down by compt but dopamine tends to have a larger diffusion radius so when it comes in

Contact with nat as well normally it will be taken up by that but because it’s blocked there is increase of dopamine as well in the synaptic cleft allowing for a dopamine action on the postsynaptic neuron so in summary snris increase noradrenaline they increase serotonin but despite not acting directly on the dopamine transporter they still increase dopamine

In the synaptic cleft as blocking nut increases dopamine now let’s look at the different kinds of snris we have duloxetine duloxetine is used in pain specifically such as chronic musculoskeletal conditions neuropathic pain fibromyalgia of course there are evidence based in anxiety disorders as well venlafaxine is a dual agent at doses of 150 or less they

Predominantly have a serotonergic effect whilst at doses greater than 225 and equal to 225 they tend to act predominantly as a non-adrenergic and dopaminergic agent and that’s why recommendations are that at doses of 225 and above one should monitor blood pressure as increased noradrenaline dopamine can be activating desvan lafaxine is a metabolite of venlafaxine

And it tends to have a non-adrenergic and dopaminergic effect at the initial dose of 50. the dose goes up to 100 and 150 milligrams one of the advantages is that it’s not broken down by the cyp enzymes in the liver and hence can be used in conditions where liver dysfunction may be an issue milnessopran is also an agent that is evidence-based in fibromyalgia uh

It has a significantly higher non-adrenergic action than the other snris and hence can be used in pain conditions such as fibromyalgia fibromyalgia does have no adrenergic pathways involved in its pathogenesis finally let’s look at the side effects and we know that snris act on serotonin noradrenaline and dopamine it results in an increase of all three but it’s

Technically not known as a triple agent such as a tricyclic because it’s not directly blocking that but rather indirectly increases dopamine through by blocking nat so can be considered as a two and a half antidepressant in a way and because of the serotonin effect in many cases can result in weight gain not in all patients but many patients can complain of it

Sexual dysfunction again because predominantly because of the serotonergic effect on the 5ht2c receptor activation a cns effect is linked to the activation and the agitation phenomenon due to increased noradrenaline and dopamine therefore when an snri started it’s important to look out for a significant insomnia significant agitation increase in anxiety that

Does not settle down racing thoughts etcetera anticholinergic side effects such as dry mouth constipation urinary retention can be an issue with snris and finally gi distress nausea vomiting diarrhea something to look out for so in summary snris increase serotonin noradrenaline and partly dopamine they’re agents that can be used in depression and anxiety but

Have particular benefit also in pain conditions so duloxetine and milnacipran are prescribed in conditions such as fibromyalgia in terms of side effects they have side effects similar to ssris but one has to be vigilant for activation phenomena greater than that of ssris because of the northern dopaminergic effect they also have greater anticholinergic side

Effects that clinicians should be mindful of so i hope that you found this summary useful see you on another hub bite take care and stay safe

Transcribed from video
Serotonin Noradrenaline Reuptake Inhibitors ( SNRIs) – Mechanism of Action and Side effects By Dr Sanil Rege’s Hub – Psychiatry Simplified