Document Detail


Effect of 3,4-diaminopyridine on rat extensor digitorum longus muscle paralyzed by local injection of botulinum neurotoxin.
MedLine Citation:
PMID:  8711757     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The actions of the K+ channel blocker, 3,4-diaminopyridine (3,4-DAP), were studied in the rat extensor digitorum longus (EDL) muscle following local inhibition of neuromuscular transmission by botulinum neurotoxin (BoNT). Local paralysis of the EDL muscle was induced by s.c. injections of BoNT serotypes A, B, E or F over the anterior tibialis muscle. One to 14 days later, the rats were anesthetized with urethane, and isometric twitch tensions following stimulation of the peroneal nerve were measured in situ. Muscles were paralyzed within 24 hr of administration of 5 mouse LD50 units (U) of BoNT/A and remained inhibited for the entire 14-day period of observation. Similar levels of inhibition, but of shorter duration, were observed after local injection of 20 U of BoNT/E, 10(4) U of BoNT/B or 20 U of BoNT/F. 3,4-DAP (4 mg/kg, i.v.) potentiated twitch tensions markedly in BoNT/A intoxicated muscle. The increase in tension developed rapidly (halftime = 5.81 +/- 0.6 min), persisted for approximately 1 hr, then decayed slowly with a halftime of 25.2 +/- 4.6 min. Subsequent administration of 3,4-DAP restored tensions to the original maxima, and this procedure could be repeated up to eight times with no decrement. The action of 3,4-DAP was comparable when given 1, 2, 3 or 7 days after BoNT/A and enhanced when administered 14 days after toxin injection. 3,4-DAP was less effective in reversing BoNT/E-induced muscle paralysis and nearly ineffective in antagonizing the paralytic actions of BoNT/B or BoNT/F. The results indicate that 3,4-DAP is of benefit in BoNT/A and BoNT/E intoxication, but is of marginal value after exposure to serotypes B and F.
Authors:
M Adler; D A Macdonald; L C Sellin; G W Parker
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  34     ISSN:  0041-0101     ISO Abbreviation:  Toxicon     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1996-09-12     Completed Date:  1996-09-12     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  237-49     Citation Subset:  IM    
Affiliation:
Neurotoxicology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
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MeSH Terms
Descriptor/Qualifier:
4-Aminopyridine / analogs & derivatives*,  pharmacology
Animals
Botulinum Toxins / antagonists & inhibitors*
Drug Interactions
Male
Muscle, Skeletal / drug effects*
Paralysis / chemically induced,  drug therapy*
Potassium Channel Blockers*
Pyridostigmine Bromide / pharmacology
Rats
Rats, Inbred F344
Chemical
Reg. No./Substance:
0/Botulinum Toxins; 0/Potassium Channel Blockers; 101-26-8/Pyridostigmine Bromide; 504-24-5/4-Aminopyridine; 54-96-6/3,4-diaminopyridine

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