Antagonism of botulinum toxin-induced muscle weakness by 3,4-diaminopyridine in rat phrenic nerve-hemidiaphragm preparations
| Autor: | J. P. Scovill, Michael Adler, Jason Piotrowski, Gerald W. Parker, Sharad S. Deshpande, Frank J. Lebeda |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_specialty
Botulinum Toxins Diaphragm Aminopyridines Pyridinium Compounds In Vitro Techniques Pharmacology Toxicology medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Isometric Contraction medicine Animals Neurotoxin Phrenic nerve Tetraethylammonium Potassium channel blocker Tetraethylammonium Compounds Calcium Channel Blockers Respiratory Paralysis Neostigmine Potassium channel Rats Surgery Phrenic Nerve chemistry Clostridium botulinum medicine.symptom medicine.drug Muscle contraction |
| Zdroj: | Toxicon. 33:527-537 |
| ISSN: | 0041-0101 |
| Popis: | The effects of the potassium channel inhibitor and putative botulinum toxin antagonist 3,4-diaminopyridine (3,4-DAP) were investigated in vitro on the contractile properties of rat diaphragm muscle. In the presence of 100 pM botulinum neurotoxin A (BoNT/A), twitches elicited by supramaximal nerve stimulation (0.1 Hz) were reduced to approximately 10% of control in 3 hr at 37 degrees C. Addition of 3,4-DAP led to a rapid reversal of the BoNT/A-induced depression of twitch tension. In the presence of 100 microM 3,4-DAP, antagonism of the BoNT/A-induced blockade began within 30-40 sec and reached 82% of control with a half-time of 6.7 min. The beneficial effect of 3,4-DAP was well maintained and underwent little or no decrement relative to control for at least 8 hr after addition. Application of 1 microM neostigmine 1 hr after 3,4-DAP led to a further potentiation of twitch tension, but this action lasted for < 20 min. Moreover, neostigmine caused tetanic fade during repetitive stimulation. In contrast to the efficacy of the parent compound, the quaternary derivative of 3,4-DAP, 3,4-diamino-1-methyl pyridinium produced little or no twitch potentiation up to a concentration of 1 mM. The potassium channel blocker, tetraethylammonium, generated a transient potentiation followed by a sustained depression of twitch tensions. It is concluded that 3,4-DAP is of benefit in antagonizing the muscle paralysis following exposure to BoNT/A. Co-application of neostigmine or tetraethylammonium with 3,4-DAP, however, appears to confer no additional benefit. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect