The protein kinase C activators, phorbol 12-myristate,13-acetate and phorbol 12,13-dibutyrate, are convulsant in the pico-nanomolar range in mice.
Administration of phorbol 12-myristate,13-acetate (PMA, 10 fmol-10 nmol) or phorbol 12,13-dibutyrate (PDB, 0.2-495 nmol) (i.c.v.) to mice induced: hindlimb scratching, tremor, myoclonic jerks, hyperlocomotion, clonic seizure, followed by death or recovery. CD50 values for clonic seizures for PMA and PDB were 1.0 pmol and 1.2 nmol. 4-alpha-Phorbol (68-686 nmol) was inactive. The effects of PDB (24-247 nmol) were reduced by pretreatment with staurosporine (30 nmol, i.c.v.). Protein kinase C activators are potent convulsants in vivo.
Smith
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SE
Department of Neurology, Institute of Psychiatry, Denmark Hill, London, U.K.
Meldrum
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BS
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003292:Convulsants / Q000494:pharmacology*; D004789:Enzyme Activation; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000008:administration & dosage / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*
D000470:Alkaloids; D003292:Convulsants; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate