[On the molecular mechanism of action of galanthamine, an antagonist of nondepolarizing muscle relaxants (author's transl)].
In clinical anaesthesia, galanthamine hydrobromide (Nivalin), an alkaloid of galanthus nivalis (common snowdrop) is used to reverse the neuromuscular blocking effect of curare-type muscle relaxants. A comparative study of the inhibition by galanthamine of acetylcholinesterase (AChE; PH 7,2; substrate; acetylthiocholine) and of pseudocholinesterase (ChE; ph 7,7; substrate: butyrylthiocholine) was carried out by means of a colorimetric assay technique at 25 degrees C. AChE (pI50 = 5.5; Ki = 5.2 X 10(-8) M) has an approximately 100-fold higher affinity to galanthamine than has ChE (pI50 = 3.7; Ki = 2.9 X 10(-6) M). The kinetic analysis of the inhibition which is instantaneously reversible upon dilution revealed a pure competitive mechanism of action for both enzymes. Supported by a calculation of the change in free binding energy (AChE: delta F = 9.9 kcal X mole-1; ChE: delta F = -7.6 kcal X mole-1), galanthamine is thought to decrease the rate of hydrolysis by a reversible binding to the anionic site of the active centre ("prosthetic inhibitor") thus impairing the formation of the enzyme-substrate complex.
D055598:Chemical Phenomena; D002621:Chemistry; D002800:Cholinesterase Inhibitors; D003124:Colorimetry; D005702:Galantamine / Q000494:pharmacology*; D027801:Galanthus; D006868:Hydrolysis; D008433:Mathematics; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors*
D002800:Cholinesterase Inhibitors; D003473:Neuromuscular Nondepolarizing Agents; D005702:Galantamine
Zum molekularen Wirkungsmechanismus von Galathamin, einem Curare-Antagonisten