28 Wrz 2018, Pią 10:32, PID: 765857
Dla dociekliwych cytuję fragment Stahl's Essential Psychopharmacology. Fourth Edition (str. 406, 407, całość tutaj: http://bucket.daz.cat/9781107025981.pdf).
Noradrenergic hyperactivity
in anxiety
Zgodnie z wytłuszczonym fragmentem kluczem byłoby to, że SNRI (lub selektywne NRI) zwiększają początkowo aktywność noradrenergiczną (jest więcej noradrenaliny w synapsie), ale w wyniku tego po jakimś czasie postsynaptyczne receptory noradrenaliny (np. beta1) odwrażliwiają się (przestają na nią reagować), co długoterminowo redukuje objawy strachu i zamartwiania się.
Noradrenergic hyperactivity
in anxiety
Norepinephrine is another neurotransmitter with
important regulatory input to the amygdala
(Figure 9-28) and to the prefrontal cortex and thalamus
in CSTC circuits (Figure 9-29). Excessive
noradrenergic output from the locus coeruleus can
not only result in numerous peripheral manifestations
of autonomic overdrive, as discussed above
and illustrated in Figures 9-8 through 9-12, but can
also trigger numerous central symptoms of anxiety
and fear, such as nightmares, hyperarousal states,
flashbacks, and panic attacks (Figure 9-28A). Excessive
noradrenergic activity can also reduce the
efficiency of information processing in the prefrontal
cortex and thus in CSTC circuits and theoretically
cause worry (Figure 9-29A). Hypothetically,
these symptoms may be mediated in part by excessive
noradrenergic input onto α1- and β1-adrenergic
postsynaptic receptors in the amygdala (Figure 9-28A)
or prefrontal cortex (Figure 9-29A). Symptoms of
hyperarousal such as nightmares can be reduced in
some patients with α1-adrenergic blockers such as
prazocin (Figure 9-28B); symptoms of fear (Figure
9-28C) and worry (Figure 9-29B) can be reduced by
norepinephrine reuptake inhibitors (also called
NET or norepinephrine transporter inhibitors).
The clinical effects of NET inhibitors can be confusing,
because symptoms of anxiety can be made
transiently worse immediately following initiation
of an SNRI or selective NET inhibitor, when noradrenergic
activity is initially increased but the postsynaptic
receptors have not yet adapted. However,
these same NET inhibitory actions, if sustained over
time, will downregulate and desensitize postsynaptic
NE receptors such as β1 receptors, and actually
reduce symptoms of fear and worry long term.
important regulatory input to the amygdala
(Figure 9-28) and to the prefrontal cortex and thalamus
in CSTC circuits (Figure 9-29). Excessive
noradrenergic output from the locus coeruleus can
not only result in numerous peripheral manifestations
of autonomic overdrive, as discussed above
and illustrated in Figures 9-8 through 9-12, but can
also trigger numerous central symptoms of anxiety
and fear, such as nightmares, hyperarousal states,
flashbacks, and panic attacks (Figure 9-28A). Excessive
noradrenergic activity can also reduce the
efficiency of information processing in the prefrontal
cortex and thus in CSTC circuits and theoretically
cause worry (Figure 9-29A). Hypothetically,
these symptoms may be mediated in part by excessive
noradrenergic input onto α1- and β1-adrenergic
postsynaptic receptors in the amygdala (Figure 9-28A)
or prefrontal cortex (Figure 9-29A). Symptoms of
hyperarousal such as nightmares can be reduced in
some patients with α1-adrenergic blockers such as
prazocin (Figure 9-28B); symptoms of fear (Figure
9-28C) and worry (Figure 9-29B) can be reduced by
norepinephrine reuptake inhibitors (also called
NET or norepinephrine transporter inhibitors).
The clinical effects of NET inhibitors can be confusing,
because symptoms of anxiety can be made
transiently worse immediately following initiation
of an SNRI or selective NET inhibitor, when noradrenergic
activity is initially increased but the postsynaptic
receptors have not yet adapted. However,
these same NET inhibitory actions, if sustained over
time, will downregulate and desensitize postsynaptic
NE receptors such as β1 receptors, and actually
reduce symptoms of fear and worry long term.
Zgodnie z wytłuszczonym fragmentem kluczem byłoby to, że SNRI (lub selektywne NRI) zwiększają początkowo aktywność noradrenergiczną (jest więcej noradrenaliny w synapsie), ale w wyniku tego po jakimś czasie postsynaptyczne receptory noradrenaliny (np. beta1) odwrażliwiają się (przestają na nią reagować), co długoterminowo redukuje objawy strachu i zamartwiania się.