UK-68,798: a novel, potent and highly selective class III antiarrhythmic agent which blocks potassium channels in cardiac cells.

UK-68,798 increased the duration and effective refractory period of cardiac action potentials recorded in vitro from canine ventricular muscle and Purkinje fibers in a concentration dependent manner from 5 nM to 1 microM. The resting membrane potential, amplitude and maximum upstroke velocity of action potentials were unaffected by UK-68,798, indicating the selective class III antiarrhythmic properties of this agent. UK-68,798 (5 nM-1 microM) increased the effective refractory period of isolated guinea pig papillary muscles at stimulation frequencies of 1 Hz and 5 Hz without influencing the conduction velocity, further confirming that UK-68,798 is devoid of class I antiarrhythmic activity including block of the sodium channel. Studies using single voltage clamped guinea pig ventricular myocytes indicated that UK-68,798 at concentrations of 50 nM and 2 microM blocks a time-dependent K+ current, with no appreciable effects on the time-independent K+ current or the inward calcium current. UK-68,798 is therefore a highly selective K+ channel blocking agent with class III antiarrhythmic properties, a profile that holds considerable promise for the therapy of life-threatening cardiac arrhythmias.

• Publication year

  1990

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1990-01-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0022-3565(25)23172-xPMID 1988662
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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