Sympatholytic

A sympatholytic (sympathoplegic) drug is a medication that opposes the downstream effects of postganglionic nerve firing in effector organs innervated by the sympathetic nervous system (SNS). They are indicated for various functions; for example, they may be used as antihypertensives. They are also used to treat anxiety, such as generalized anxiety disorder, panic disorder and PTSD. In some cases, such as with guanfacine, they have also shown to be beneficial in the treatment of ADHD.

Antiadrenergic agents inhibit the signals of epinephrine and norepinephrine. They are primarily postsynaptic adrenergic receptor antagonists (alpha and beta adrenergic receptor antagonists, or "blockers"), inhibiting the downstream cellular signaling pathways of adrenergic receptors. However, there are exceptions: guanfacine and clonidine are adrenergic agonists at the α2 receptor; since this receptor is located presynaptically, agonism at this receptor inhibits the presynaptic release of adrenaline and noradrenaline, preventing postsynaptic adrenergic receptor activation and downstream signaling.

Another way to inhibit adrenergic receptor signaling is by blocking the synthesis of catecholamines. Methyltyrosine, for example, inhibits one of the key enzymes in the pathway: tyrosine hydroxylase.

For neurotransmitters to be released, they first must be stored in synaptic vesicles. Reserpine works by inhibiting VMAT, preventing the storage of neurotransmitters into synaptic vesicles. If VMAT is inhibited, neurotransmitters won't be released into the synaptic cleft, thereby inhibiting their downstream effect.

Other drugs are preferentially toxic to sympathetic neurons. One method of obtaining such specificity is to exploit drugs that are substrates for a transporter preferentially expressed on sympathetic terminals, such as the norepinephrine transporter. Such transports allows the drugs to accumulate within sympathetic neurones, where they can act to inhibit sympathetic function. Such drugs include bretylium, guanethidine and 6-hydroxydopamine.

Many antiadrenergic agents used as antihypertensives include:

There is clear evidence from many controlled trials in the past 25 years that beta blockers are effective in anxiety disorders, though the mechanism of action is not known.

Some people have used beta blockers for performance type social anxiety, or "stage fright." In particular, musicians, public speakers, actors, and professional dancers, have been known to use beta blockers to avoid stage fright and tremor during public performance and especially auditions. The physiological symptoms of the fight/flight response associated with performance anxiety and panic (pounding heart, cold/clammy hands, increased respiration, sweating, etc.) are significantly reduced, thus enabling anxious individuals to concentrate on the task at hand. Stutterers also use beta blockers to avoid fight/flight responses, hence reducing the tendency to stutter.