Possible Interaction: Epinephrine and Tetrodotoxin

“At some concentrations, the addition of sodium octyl sulfate increased the duration of block from TTX plus epinephrine, and epinephrine increased that from TTX plus CPEs.”

“In those studies, epinephrine combined with TTX prolonged blocks more than 10-fold, while reducing systemic toxicity.”

“Coinjection of epinephrine with tetrodotoxin prevented decreases in brain blood flow.”

“Coinjection of epinephrine with tetrodotoxin prevented tetrodotoxin-induced increases in perisciatic muscle blood flow over time and did not alter sciatic nerve blood flow.”

“Conclusions:Vasoconstriction in the perisciatic muscles by epinephrine may contribute to the prolongation of tetrodotoxin-induced sciatic nerve blocks and the reduction of systemic toxicity of tetrodotoxin.”

“It was found that sciatic nerve block duration could be greatly increased and systemic toxicity greatly decreased if epinephrine was injected with tetrodotoxin.”

“The mechanism that underlies epinephrine-mediated prolongation of tetrodotoxin nerve blocks is not known, but indirect evidence suggests that epinephrine may slow the clearance of tetrodotoxin from the site of injection.”

“Superfusion with tetrodotoxin (1 μmol 1−1) for 12 min elicited a prompt and sustained decrease (−70%) in the release rates of dopamine and adrenaline.”

“ Tetrodotoxin (1 microM) perfused into the right rostral ventrolateral medulla gradually decreased basal levels of L-DOPA by 25%; it decreased basal levels of noradrenaline and adrenaline by 25-30% and dopamine levels by 40%.”

“ Epinephrine reduced measures of systemic distribution and increased the median lethal dose of tetrodotoxin from 40 to 53.6 nmole/kg, thus more than quadrupling the therapeutic index.”

“ Epinephrine reduced the median effective concentration of tetrodotoxin for nociception from 37.6 to 11.5 [micro sign]M and prolonged its duration, such that reversible blocks lasting >13 h were achieved.”

“In a subpopulation of neurons (3/9) from P15-18 rats, EPI increased both the amplitude and frequency of miniature IPSCs (mIPSCs) recorded in the presence of tetrodotoxin (TTX) and under conditions where postsynaptic EPI effects were blocked, suggesting activation of adrenoceptors on presynaptic terminals in these cells.”

“The force recovery induced by salbutamol, adrenaline and insulin was suppressed by pre‐exposure to ouabain (10(‐5) M for 10 min or 10(‐3) M for 1 min) as well as by tetrodotoxin (10(‐6) M).”

“4 Tetrodotoxin (780 nM) partially reduced the contraction induced by noradrenaline or adrenaline but atropine (500 nM) did not.”

“ Adrenaline (3X10(-5)-3X10(-4)M) markedly depressed the peak amplitude and maximum rate of rise of both TEA-potential and Ca-potential produced either in TEA solution containing TTX or in the isotonic CaCl2 solution.”