YS-035 hydrochloride

Inhibition of potassium outward currents and pacemaker current in sheep cardiac Purkinje fibres by the verapamil derivative YS 035.[Pubmed:1775198]

Naunyn Schmiedebergs Arch Pharmacol. 1991 Dec;344(6):653-61.

The electrophysiologic mode of action and potency of the verapamil derivative YS 035 (N,N-bis-(3,4-dimethoxyphenethyl)-N-methyl amine) were investigated in sheep cardiac Purkinje fibres. Action potential duration measured at a repolarization level of -60 mV (APD-60) and membrane currents recorded with the two-microelectrode voltage-clamp technique were evaluated. At 10 mumols/l YS 035 APD-60 was increased to about 115% of reference. Prolongation measured as percentage of the respective control exhibited on the average no dependence on stimulation frequency (0.17-2 Hz). At 100 mumols/l membrane became depolarized to about -50 mV and action potentials could no longer be elicited. Further study was focussed on effects on outward currents, mostly activated at a frequency of 0.05 Hz. Transient outward current (ito) was completely blocked at 100 mumols/l and half-maximal inhibition occurred at about 14 mumols/l. Inwardly rectifying potassium current (ik1) was reduced to 47% of reference at 100 mumols/l. An initially activating outward current at positive membrane potentials (iinst) was reduced to 73% at 100 mumols/l. Time-dependent (delayed) outward current (iK) was on the average not affected up to 100 mumols/l. Besides inhibition of repolarizing outward currents YS 035 completely blocked pacemaker current (if) at 100 mumols/l and half-maximal reduction was achieved at 5 mumols/l. YS 035 (1-100 mumols/l) did not clearly affect time constants of activation at selected test potentials (IK: +35 mV; if: -90 mV) or inactivation (ito: 0 mV). Voltage-dependent control mechanisms of currents (ito, if) were not influenced by YS 035 but the amount of available current was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Properties of a new calcium ion antagonist on cellular uptake and mitochondrial efflux of calcium ions.[Pubmed:6721841]

Biochem J. 1984 Mar 15;218(3):899-905.

Compound YS 035 [NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine] is a new synthetic compound capable of inhibiting Ca2+ uptake by different cells. The inhibition of Ca2+ uptake by muscle cells isolated from chicken embryo is dose-dependent in the compound YS 035 concentration range 10-30 microM. The new compound also inhibits Ca2+ entry into rat brain synaptosomes and less effectively into baby-hamster kidney cells. Compound YS 035 partially inhibits the slow Ca2+ release induced by Ruthenium Red and the rapid Na+-dependent efflux from heart mitochondria. The inhibition of the Na+/Ca2+ exchange appears to be of a non-competitive type with an apparent Ki of 28 microM. The new Ca2+ antagonist totally inhibits the Ca2+ efflux from liver mitochondria induced by Ruthenium Red, but it does not affect the release induced by uncoupler, respiratory inhibitor or chelator, nor the mitochondrial ATP synthesis and membrane potential. The properties shown by the new compound indicate it to be a Ca2+ antagonist and a useful tool for studies on the mitochondrial Ca2+ transport.