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Biomedical subjects

T Ban

Publications and source records attributed to T Ban.

At least 253 records · Page 14Linked to original sources
PubMed1981

Effects of various structurally related beta-adrenoceptor blocking agents on maximum upstroke velocity of action potential in guinea-pig papillary muscles.

The effects of indenolol (7.0-100 mumol/l), befunolol (15.3-250 mumol/l), metoprolol (58.4-1000 mumol/l), Kö707 (7.3-100 mumol/l), D-25 (3.7-100 mumol/l) and Kö1313 (73.9-1000 mumol/l) on action potentials were investigated in isolated guinea-pig papillary muscles. All these aryloxyisopropylaminopropanol derivatives produced a concentration-dependent reduction of V max at a basic rate of 1 Hz. The reduction was less prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function. The results, together with those reported previously (Sada and Ban 1980, 1981), revealed: (1) a significant correlation between potencies of these derivatives for depression of V max at 0.027, 0.25, 1 and 5 Hz and their log n-octanol/water partition coefficients (log P): (2) The time constants of recovery were relatively concentration independent and correlated significantly with the molecular weights. The results suggest that the potency of these drugs for the depression of V max was mainly determined by log P, being modified secondarily by the time constants of recovery which are intimately associated with the molecular weights.

Action Potentials↗
PubMed1981

Negative inotropic effects and the hydrophobicity of beta-adrenergic blocking agents.

The negative inotropic actions of 12 beta-adrenergic blocking agents, all of which are aryloxyisopropylaminopropanols were studied in isolated left atria from reserpinized guinea-pig hearts. At concentrations between 10 and 1000 microM, all these drugs, with the exception of atenolol, reduced the contractile force by more than 40%. The following order of potency, as measured as ED40, was thus derived:propranolol, alprenolol, D-25, Ko 707, pindolol, oxprenolol, Kö 592, befunolol, metoprolol, Kö 1313, acebutolol and atenolol. On the other hand, the order of the octanol/water partition coefficient (P) was as follows: propranolol, alprenolol, D-25, Kö 707, Kö 592, oxprenolol, befunolol, acebutolol, metoprolol, pindolol, Kö 1313 and atenolol. A significant correlation was found between log l/ED40 and log P. The results indicate that hydrophobicity is a major determinant for the negative inotropic effects of these beta-adrenergic agents.

Adrenergic beta-Antagonists↗
PubMed1981

Frequency-dependent block of nerve conduction by beta-adrenergic blocking agents.

We investigated frequency-dependent effects of 12 beta-adrenergic blocking agents, all 1-aryloxy-3-isopropylaminopropane-2-ol derivatives, on the height of the compound action potential of frog sciatic nerves, using sucrose gap techniques. The order of 1/ED50 of these agents at 0.1 Hz for the reduction of the height was: indenolol greater than D-25 greater than propranolol greater than alprenolol greater than pindolol greater than toliprolol greater than oxprenolol greater than befunolol greater than Kö1313 greater than acebutolol greater than metoprolol greater than atenolol. The order was similar also at 100 Hz. Logarithms of n-octanol/buffer partition coefficients (log P) correlated well with log (1/ED50) at either 0.1, 1, 10 or 100 Hz (p less than 0.01). The order of log [(ED50)0.1 Hz/(ED50)100 Hz] was oxprenolol greater than befunolol greater than propranolol greater than alprenolol greater than toliprolol greater than indenolol greater than Kö1313 greater than pindolol greater than D-25. Molecular weight of these drugs correlated well with the difference of log (ED50)100 Hz and log (ED50)10 Hz from log (ED50)0.1 Hz (P less than 0.05). The results indicate that the local anesthetic potency of these beta-blockers is mainly determined by the lipid solubility of the drugs, being modified by the frequency-dependent component of action which is related to the molecular weight.

Action Potentials↗
PubMed1980

Effects of tocainide and lidocaine on the transmembrane action potentials as related to external potassium and calcium concentrations in guinea-pig papillary muscles.

Effects of lidocaine and tocainide on transmembrane potentials were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution containing either 5.4, 2.7, 10.0 or 8.1 mmol/l potassium concentration, [K]0. The last solution applied contained either 1.8 (normal [Ca]0) or 7.2 mmol/l [Ca]0 (high [Ca]0. The concentrations of lidocaine and tocainide used were 18.5, 36.9 and 73.9 mumol/l and 43.7, 87.5 and 174.9 mumol/l in 5.4 mmol/l [K]0 solution and 36.9 and 87.5 mumol/l in the other solutions, respectively. At the driving rate of 1 Hz in 5.4 mmol/l "K]0 solution, both drugs produced dose-dependently a reduction of maximum rate of rise of action potential (Vmax), together with a prolongation of the relative refractory period. Vmax decreased progressively as the driving rate was increased from 1 Hz (for lidocaine) and from 0.25 Hz (for tocainide) to 5 Hz. This action was accentuated dose-dependently. A slow component (time constant tau = 232 ms for lidocaine, 281--303 ms for tocainide) and slower component (tau = 2.1--3.8 s for tocainide) of the recovery (reactivation) of Vmax were observed in premature responses at 0.25 Hz and in the first response after interruption of the basic driving rate at 1 Hz. All these effects were accentuated with rising [K]0 and attenuated in the high [Ca]0 solution. Both drugs abbreviated the action potential duration at 50% (APD50) and 90% (APD90) levels at 5.4, 8.1 and 10.0 mmol/l [K]0 but not at 2.7 mmol/l [K]0 nor a high [Ca]0 at 1 Hz. These [K]0-dependent effects of lidocaine on Vmax were successfully simulated by the model proposed by Hondeghem and Katzung (1977), with a slight change in parameter values. The mode of interaction of lidocaine with sodium channels in the open, closed and rested states was deduced from these results.

Action Potentials↗
PubMed1980

Effects of mexiletine on transmembrane action potentials as affected by external potassium concentration and by rate of stimulation in guinea-pig papillary muscles.

1. The effects of mexiletine and quinidine were compared on transmembrane potentials in guinea-pig papillary muscles, using conventional microelectrode techniques. 2. Mexiletine (23.1 mumol/l) decreased the maximum rate of rise of the action potential (Vmax) and increased the ratio of the effective refractory period to the action potential duration at 90% repolarization level (ERP/APD90); these effects were prominent with elevation of the external potassium concentration ([K]o) from 2.7 to 5.4, 8.1 and 10.0 mmol/l. 3. The percentage decrease in Vmax induced by 5 and 10 mumol/l of quinidine was approximately constant in 2.7, 5.4 and 10.0 mmol/l [K]o solutions. 4. The decrease in Vmax produced by mexiletine was progressively increased as the driving rate was raised from 0.25 to 5Hz. This rate-dependent change was pronounced when the concentration was raised from 23.1 to 46.2 and 92.4 mumol/l. 5. Mexiletine in concentrations of 23.1 and 92.4 mumol/l delayed the recovery of Vmax in a premature action potential to the level of Vmax in the conditioning action potentials at the driving rate of 0.25 Hz. 6. It appears that mexiletine exerts its anti-arrhythmic action by a selective depressant effect on depolarized cells (high [K]0) and cells with high frequency discharges, as is the case with lignocaine.

Action Potentials↗
PubMed1980

Naltrexone in chronic schizophrenia. Results of a clinical trial.

A 4-week clinical trial, including a 1-week placebo washout period, assessed the antipsychotic activity of naltrexone in 'newly admitted', actively hallucinating, chronic schizophrenics. Chronic naltrexone administration was found to benefit 2 patients and to be of no value in 3 patients. Responsive patients differed from non-responders by the presence of hallucinations despite adequate neuroleptic maintenance therapy and an appropriate response to pathological hallucinatory experience. On the basis of these findings, the possibility of a naltrexone-responsive schizophrenic subgroup was considered.

Adult↗
PubMed1980

Effects of acebutolol and other structurally related beta adrenergic blockers on transmembrane action potential in guinea-pig papillary muscles.

The effects of acebutolol (13-134 microM), pindolol (10-50 microM), oxprenolol (16-66 microM) and (+) and (-)-Kö592 (39-193 microM) on action potentials were investigated in isolated guinea-pig papillary muscles. All the drugs reduced Vmax at 1 Hz, dose-dependently. The reduction was less prominent with prolongation of the interstimulus interval until there was virtually no reduction. The time course of recovery of Vmax during diastole was studied by assessing Vmax in premature responses at 0.1 Hz or in responses after interrupting driving stimuli at 1 Hz. Time constants of recovery thus estimated were 12 to 14 sec for acebutolol and pindolol, 3 to 6 sec for oxprenolol and 0.7 to 1 sec for (-)-Kö592. The reduction of Vmax was rate dependent for all the drugs, and at 5 Hz, the order of potency was oxprenolol > pindolol > acebutolol congruent to (-)- and (+)-Kö592. The most potent was alprenolol (3.5-17.5 microM), which we have already studied in detail. At 1 Hz or lower, the action potential duration was shortened by application of all the compounds mentioned except acebutolol, but tended to be longer than in control, at higher rates for all the drugs. We conclude that molecular bulkiness and dimension may be associated with the time constant of recovery, whereas the potency at high driving rates may be correlated roughly linearly with the lipid solubility of the agents.

Acebutolol↗
PubMed1979

Effect of procainamide on transmembrane action potentials in guinea-pig papillary muscles as affected by external potassium concentration.

Effects of procainamide (PA), 0.18, 0.37 and 0.74 mmol/l, on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution (external K concentration, [K]0 = 5.4 mmol/l) at the basic driving rate of 1 Hz. PA, at 0.37 mmol/l, significantly reduced the maximum rate of rise of action potential (Vmax) with no change in the resting potential. When 2.7 mmol/l [K]0 of the superfusate was exchanged for 15 mmol/l [K]0 solution a decrease in Vmax induced by 0.37 mmol/l PA became more prominent with decrease in resting potential. The reduction of Vmax at steady state was less at lower driving rates (0.25 and 0.5 Hz) and more at higher driving rates (2-5 Hz) than at 1 Hz in 2.7, 5.4 and 10.0 mmol/l [K]0 solution. Such changes were enhanced concentration-dependently by PA at 5.4 mmol/l [K]0. Also, the changes became more significant with an increase in [K]0 from 2.7 mmol/l to 5.4 mmol/l and then to 10.0 mmol/l. The recovery process of Vmax proceeded with two components. The time course of the slow component seen in the Vmax of the first response after interruption of basic driving stimulation at 1 Hz, followed an approximate monoexponential function. The time constants were 6.3, 4.4 and 5.8 s in the presence of 0.18, 0.37 and 0.74 mmol/l PA at 5.4 mmol/l [K]0 and 3.4 and 3.7 s both in the presence of 0.37 mmol/l PA at 2.7 and 10.0 mmol/l [K]0. Vmax values after 30 or 60 s interruption of stimulation were 80-92% of the predrug Vmax value at 1 Hz. The time constants of the first component, estimated by the peeling-off methods at the driving rate of 0.1 Hz, were 11, 31 and 5-22 ms in the presence of 0.37 mmol/l at 5.4, 10.0 and 2.7 mmol/l [K]0 and did not differ significantly from the time constants in control preparations. The results were found to be consistent, to a certain extent, with the model proposed by Hondeghem and Katzung (1977).

Action Potentials↗