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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Ketamine and ditran block end-plate ion conductance and [3H]phencyclidine binding to electric organ membrane.

R L Volle, K A Alkadhi, D D Branisteanu, L S Reynolds, P M Epstein, H Smilowitz, J J Lambert and E G Henderson
Journal of Pharmacology and Experimental Therapeutics June 1982, 221 (3) 570-576;
R L Volle
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K A Alkadhi
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D D Branisteanu
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L S Reynolds
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P M Epstein
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H Smilowitz
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J J Lambert
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E G Henderson
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Abstract

Alterations by ketamine (10-100 microM) and ditran (50-100 microM) of end-plate currents were studied using transected cutaneous pectoris muscles. Both drugs reduced peak current and shortened the time constant for end-plate current decay (tau). Ketamine was more effective at pH 5.3 than at 7.4 or 9.1. Recovery from blockade was asymmetrical in that tau recovered more quickly than did peak current when the drugs were removed from the bath. By contrast, 4-aminopyridine antagonized the depression of peak current by ketamine, but not the reduction of tau. Both ketamine and ditran disrupted the voltage dependence of tau. The binding to microsacs prepared from electric organs of [3H]phencyclidine ([3H]PCP) was blocked by ketamine and ditran. In microsacs treated with carbachol, the IC50 for ketamine block of [3H]PCP binding was 6.6 X 10(-6) M. For ditran, the IC50 for block of [3H]PCP binding in the presence of carbachol was 1.7 X 10(-6) M. The binding of [alpha-125I]bungarotoxin to the microsacs or to the cultured chick myotubes was reduced only slightly by ketamine. Because ketamine has no effect on transmitter release and little effect on [alpha-125I]bungarotoxin binding, it is concluded that, like PCP, ketamine and ditran block open channels in the end-plate. In addition, the asymmetrical recovery of end-plate current parameters suggests that ketamine may block closed channels. The recovery from block of closed channels (caused by either a direct action on closed channels or a very slow channel unblocking rate) proceeds more slowly than does the block of open channels.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 221, Issue 3
1 Jun 1982
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Abstract

Ketamine and ditran block end-plate ion conductance and [3H]phencyclidine binding to electric organ membrane.

R L Volle, K A Alkadhi, D D Branisteanu, L S Reynolds, P M Epstein, H Smilowitz, J J Lambert and E G Henderson
Journal of Pharmacology and Experimental Therapeutics June 1, 1982, 221 (3) 570-576;

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Abstract

Ketamine and ditran block end-plate ion conductance and [3H]phencyclidine binding to electric organ membrane.

R L Volle, K A Alkadhi, D D Branisteanu, L S Reynolds, P M Epstein, H Smilowitz, J J Lambert and E G Henderson
Journal of Pharmacology and Experimental Therapeutics June 1, 1982, 221 (3) 570-576;
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