Pharmakologie der Botulinumtoxine

Zusammenfassung

Therapeutische Präparationen von Botulinumtoxin (BT) bestehen aus Botulinum Neurotoxin (BNT), Komplexproteinen und pharmazeutischen Hilfsstoffen. Je nach Zielgewebe kann BT die cholinerge neuromuskuläre oder die cholinerge autonome Transmission an Schweißdrüsen, Tränendrüsen, Speicheldrüsen und glatter Muskulatur unterbrechen. Weitere direkte BT-Wirkungen lassen sich an Muskelspindelorganen nachweisen. Indirekte Effekte auf das Zentralnervensystem sind zahlreich, direkte sind nach intramuskulärer Injektion bisher nicht beschrieben worden.

In Deutschland wird BT Typ A als Botox®, Dysport® und Xeomin® und BT Typ B als NeuroBloc® angeboten. Nebenwirkungen der BT-Therapie können in obligate, lokale und systemische unterteilt werden. Die Nebenwirkungsprofile der verschiedenen BT Typ A-Präparationen sind weitgehend identisch. Bei BT Typ B zeigen sich häufig zusätzlich systemische autonome Nebenwirkungen. Langzeitbehandlungen rufen keine zusätzlichen Nebenwirkungen hervor. Gegen BNT können Antikörper gebildet werden, die die biologische BNT-Wirkung ganz oder teilweise blockieren. Das Risiko einer BNT-Antikörperbildung hängt wesentlich ab von der BNT-Menge, die bei jeder BT-Injektionsserie appliziert wird, vom Intervall zwischen den BT-Injektionsserien und von der Spezifischen Biologischen Aktivität (SBA) der BT-Präparation. Diese beträgt bei NeuroBloc® 5, bei Botox® 60, bei Dysport® 100 und bei Xeomin® 167 MUE/ng BNT (MU-E: Equivalenz-Mauseinheiten). Xeomin® dürfte daher die günstigsten Antigenitätseigenschaften aufweisen. Entsprechende klinische Erfahrungen stehen jedoch noch aus.

Summary

Therapeutic preparations of botulinum toxin (BT) consist of botulinum neurotoxin (BNT), complexing proteins and excipients. Depending on the target tissue, BNT blocks cholinergic neuromuscular or cholinergic autonomous transmission controlling sweat, lacrimal and salival glands as well as smooth muscles. Additional direct effects target muscle spindle organs. Indirect effects on the central nervous system are numerous, direct ones have not been reported after intramuscular application.

In Germany BT type A is being distributed as Botox®, Dysport® and Xeomin®, BT type B as NeuroBloc®. Acute adverse effects of BT can be obligate, local or systemic. Adverse effect profiles of the different preparations are similar. BT type B, however, often produces additional systemic autonomic adverse effects. Long-term application does not produce additional adverse effects.

BNT can be partially or completely blocked by antibodies. The major risk factors are the amount of BNT applied at each injection series, the interval between the injection series and the specific biological potency (SBP) of the BT preparation used. The SBP is 5 for NeuroBloc®, 60 for Botox®, 100 for Dysport® and 167 MU-E/ng BNT for Xeomin® (MU-E: equivalence mouse units). Xeomin® should therefore have a particular low antigenicity. Clinical data, however, are still lacking.

Schlüsselwörter - Botulinumtoxin - Therapie - Pharmakologie - Wirkungsmechanismen - Antikörper - unerwünschte Wirkungen

Keywords

Botulinum toxin - therapy - pharmacology - mode of action - antibodies - adverse effects

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