Antisympathotonic

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Antisympathotonics are active ingredients that reduce the sympathetic tone, i.e. the activity of the sympathetic nervous system .

Due to their associated blood pressure lowering effect, they are mainly used as antihypertensive agents, although today they are no longer to be regarded as the drug of choice due to their poor tolerance. Historically, however, they were the first option for effective high blood pressure therapy in human medicine. In veterinary medicine, however, they have always been of no practical importance.
Overall, however, there was again a slight increase in medical prescriptions for antisympathotonics in 2005 : Compared to the previous year, prescriptions rose by 8.8% to 215.5 million DDD . The main driver here was moxonidine with an increase of 16.9%, which is currently (2006) the dominant active ingredient of the otherwise quite anachronistic drug group.

history

The effects of α-methyldopa were first demonstrated in 1960 by John Alexander Oates . This was also confirmed by comparative studies with other established antihypertensive drugs .

The effect of clonidine, on the other hand, was discovered by accident by Helmut Stähle . In the 1960s, he was researching a remedy for colds. For this he used the active ingredient ST 155, which is synthesized from imidazoline . During research, however, steels mainly found an antihypertensive effect. Nowadays, clonidine is available on the German market as Catapresan . Because of side effects, the less dangerous clonidine-related moxonidine was developed. It has been sold under the name Cynt since 1991 .

Reserpine, on the other hand, was used historically in East Asia to heal various diseases. The antihypertensive and antipsychotic effects were discovered by Katrick Chandra , Bose and Bakil. Guanethidine developed RP Mull in 1957/58.

Mechanism of action

There are three important pharmacological mechanisms for reducing sympathetic tone, all of which reduce the presynaptic release of the messenger substance norepinephrine :

  1. The re- uptake of noradrenaline in the vesicles of the presynaptic sympathetic nerve endings is inhibited, the noradrenaline storage is “depleted”. One drug that works in this way is reserpine .
  2. The release of noradrenaline from the nerve endings is reduced. Guanethidine, for example, works according to this method .
  3. Central α2 adrenoceptors with an inhibitory effect on transmitter release are activated. This mechanism of action is represented, for example, by clonidine and probably also by methyldopa .

The lowering of the sympathetic tone takes place indirectly via the lowering of the noradrenaline release by reducing the stimulation of the postsynaptic adrenoceptors .

Problems with antisympathotonics

In practice, the use of antisympathotonics is severely restricted due to their very poor tolerance. Because of their side effects, they should not be used as primary antihypertensive therapy. They are most suitable for use in combination therapy. The exact side effects vary from drug to drug.

In a sick sinus syndrome , a bradycardia or heart block second or third degree, as well as depression or hepatic insufficiency antisympathotonics are contraindicated.

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Individual evidence

  1. ↑ Lüllmann, Mohr, Wehling: Pharmacology and Toxicology . Thieme, Stuttgart, 2006. ISBN 3133685163 .
  2. ^ Löscher, Ungemach, Kroker: Pharmacotherapy in domestic and farm animals . Blackwell Wissenschafts-Verlag, Berlin / Vienna, 1999. ISBN 3826332865 . P. 57.
  3. Jump up : Antihypertensive drugs . In: Schwabe, Paffrath: Drug Ordinance Report 2006 . Springer, Berlin, 2006. ISBN 3540343695 . Ss. 418-420.
  4. ^ Wolf-Dieter Müller-Jahncke , Christoph Friedrich , Ulrich Meyer: Medicinal history . 2., revised. and exp. Ed. Wiss. Verl.-Ges, Stuttgart 2005, ISBN 978-3-8047-2113-5 , pp. 171 .