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Caramiphen: a non-opioid antitussive with potent anticonvulsant properties in rats.

Abstract
The effect of the non-opioid antitussive caramiphen was studied in the rat maximal electroshock test. Caramiphen produced a dose- and time-dependent blockade of tonic hindlimb extension and was nearly twice as potent as the prototypical anticonvulsant drug diphenylhydantoin. Pretreatment with a subthreshold-effective dose of caramiphen potentiated the anticonvulsant effects of diphenylhydantoin, lowering its ED50 33-fold. The anticonvulsant effects of caramiphen were not associated with its cholinolytic activity since (a) its anticonvulsant effects were not antagonized by physostigmine and (b) the more potent cholinolytic atropine was only weakly effective against maximal electroshock convulsions when tested at doses 25 times the minimally effective dose of caramiphen. Anticonvulsant effects of caramiphen were associated with minimal behavioral impairment. The results demonstrate that caramiphen is a potent anticonvulsant against generalized convulsions and, like other non-opioid antitussives, will enhance the anticonvulsant properties of diphenylhydantoin. It is suggested that the anticonvulsant effects of caramiphen result from specific binding to brain receptors labelled by the non-opioid antitussive dextromethorphan, and that the interactions with diphenylhydantoin involve allosteric interactions between the different binding sites.
AuthorsF C Tortella, J M Witkin, J M Musacchio
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 155 Issue 1-2 Pg. 69-75 (Oct 11 1988) ISSN: 0014-2999 [Print] Netherlands
PMID3243332 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Anticonvulsants
  • Antitussive Agents
  • Cyclopentanes
  • Phenytoin
  • Atropine
  • caramiphen
  • Physostigmine
Topics
  • Animals
  • Anticonvulsants
  • Antitussive Agents (pharmacology)
  • Atropine (pharmacology)
  • Behavior, Animal (drug effects)
  • Cyclopentanes (pharmacology)
  • Electroshock
  • Injections, Subcutaneous
  • Male
  • Phenytoin (pharmacology)
  • Physostigmine (pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Time Factors

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