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PubMed1975

The effect of procaine on the mechanical and electrical activities of the smooth muscle cells of the guineal pig urinary bladder.

Procaine (1-15 mM) enhanced the spontaneous contractions of the urinary bladder smooth muscle. When a low concentration of procaine was added to normal Krebs solutions, spontaneous rhythmic contractions were enhanced. On increasing the concentration of procaine, a rise in tone (resting tension) of the preparation was observed and gradually decreased with time. The action of procaine of enhancing spontaneous contraction was observed in Na-deficient (sucrose substitutiona) and Na-free (Tris substitution) Krebs solutions. Tetrodotoxin (3 X 10(-7) G/M) DID NOT INHIBIT THE EFFECT OFPROCAINE ON MECHANICAL RESPONSE. In normal Krebs solution, procaine depolarized the membrane and increased spike frequency. The peak potential of the spike increased at 1 mM of procaine, but was suppressed at concentrations of more than 5mM. After-hyperpolization of the spike was diminished by procaine and spike duration was prolonged. The maximum rate of rise of the spike was increased immediately after application of 1 mM of procaine, but decreased wiith time. The maximum rate of fall of the spike was markedly decreased by procaine. Relative membrane resistance was increased by the application of procaine. From these results it is suggested thatprocaine mainly reduces K conductance and causes depolarization, and that enhanced spontaneous contractions are caused by depolarization and increased spike activity.

Animals↗
PubMed1976

Relationship between effects of procaine and Ca on spontaneous electrical and mechanical activities of the smooth muscle cells of the guinea pig urinary bladder.

The relationships between the effects of procaine and those of Ca on the spontaneous electrical and mechanical activities of smooth muscle cells of the guinea pig urinary bladder were studied using both microelectrode and sucrose gap methods. Procaine(1, 7, and 15mM) depolarized the membrane and increased spontaneous spike freqency. The maximum rates of rise and fall and the after-hyperpolarization of the spike decreased. Enhanced spontaneous rhythmic contractions accompanied these membrane activities (1 mM). The tone of the preparation (resting rension) increased transiently and decreased gradually (7-15mM). These procaine effects were suppressed by the application of excess Ca (7.5 mM). The increased electrotonic potential induced by 7mM procaine was reduced by the addition of 7.5 mM Ca. Reduction of Ca concentration (0.8 and 0 mM) IN Krebs solution containing procaine further depolarized the membrane and decreased the spike amplitude. In Ca-deficient solution, the enhanced rhythmic contractions induced by procaine were slightly reduced. Compound D600 (1-3mg/1), manganese ion (Mn) (1-3 mM), and cobalt ion (CO) (1-3 MM) inhibited the effects of procaine on spike discharges and mechanical responses. From these results it is concluded that procaine action is related to that of Ca which controls the membrane permeability, since procaine depolarizes the membrane by reducing K conductance. Furthermore, action potentials observed in the Krebs solution containing procaine are considered to be Ca spikes, which seem to play an important role in excitation-contraction coupling in the guinea pig urinary bladder smooth muscle.

Action Potentials↗
PubMed1976

Inhibitory effects of procaine on the electrical and mechanical activities of the smooth muscle cells of the guinea pig urinary bladder.

Modification of the effects of K, Ca, acetylcholine and rapid cooling by procaine were examined in the smooth muscle of the guinea pig urinary bladder. Contraction enhancement by procaine was observed in 5.9 mM K - and 23.6 mM K-Krebs solution but was not confirmed in 59 mM K solution. Procaine enhanced contraction in relation to membrane activities. Relationships between membrane potential and K concentration showed that procaine reduced K conductance. This effect decreased as K concentration increased. K-induced contracture was inhibited by procaine at 37 degrees and 10 degrees C. Procaine inhibited Ca- and acetylcholine-induced contractions in isotonic K2SO4-Locke solution. Rapid cooling contracture, initiated by lowering the temperature of the solution from 36 +/- 1 degrees C to 12 +/- 2 degrees C within 30 sec, was inhibited by procaine. From these results, it is concluded that procaine has an inhibitory effect on Ca permeation through the cell membrane and on Ca release from sequestered sites, and it is confirmed that procaine enhancement of spontaneous contractions is related to the spike activity resulting from depolarization which is caused by reduction of K conductance (KURIHARA, 1975). The mechanism of the procaine effect is discussed in relation to excitation-contraction coupling in the guinea pig urinary bladder.

Acetylcholine↗
PubMedDate not supplied

Development of thermotolerance in CHO cells: modification by procaine.

We have tested the reported ability of procaine to inhibit the induction and the development of thermotolerance in Chinese hamster ovary cells. Thermotolerance was induced either by hyperthermia alone (10 min, 45 degrees C) or by combining hyperthermia and procaine (5 min, 45 degrees C + 10 mM procaine) with heating times adjusted to yield similar cell survival after the conditioning treatments. Both the kinetics of thermotolerance development in fresh medium without procaine and the magnitude of thermotolerance 6 h after heat conditioning were similar for the two treatment groups. Development of thermotolerance in the presence of procaine was tested by adding the drug at 5 or 10 mM to culture medium between, but not during two fractionated heat treatments. Thermotolerance development was observed even in the presence of 10 mM procaine, but only if cell survival was corrected for the 37 degrees C-procaine toxicity. Complete survival curves of cells incubated for 6 h at 37 degrees C in 7.5 mM procaine between heat conditioning and test heating showed a D0 that was only 35 per cent lower than that of thermotolerant controls. The data are consistent with the reported sensitization to heat killing by procaine, but show that thermotolerance induction and development were only minimally perturbed by procaine.

Animals↗
PubMed1975

Site of action and active form of procaine in squid giant axons.

The active form of procaine and its, site of action on the nerve membrane have been studied in intact and internally perfused squid giant axons. Voltage clamp techniques were employed to measure the masimum values for peak sodium conductance and for steady-state potassium conductance as an index of activity. Changes in internal pH between 7 and 8 do not influence the blocking potency of procaine applied internally. This result, when compared to theoretical curves, is only compatible with the notion that the charged form of procaine present inside is the active form. If one momentarily arrests internal perfusion during an experiment in which procaine is being applied externally, the conductance block is significantly potentiated. When procaine is applied simultaneously to both external and internal phases, most of the block can be reversed by washing out the inside at a time when the outside is still being perfused with procaine. If one reverses this procedure, very little recovery is noted with removal of procaine from the external phase. The rate of recovery from the procaine blockage is much faster in internally perfused axons. These three observations support the notion that procaine acts from inside the nerve membranes. It is concluded that procaine, as other lidocaine derivatives studied previously, acts from the internal nerve membrane surface in the charged form.

Animals↗
PubMed1982

Ganglionic blockade by procaine in the presence of pentobarbital and diethyl ether.

The interactions of procaine with pentobarbital and diethyl ether were observed on the isolated stellate ganglion of the hamster. Each drug reduced the amplitude of the compound postganglionic action potential induced by stimulation of the preganglionic nerve at 0.2 Hz. The slopes of the concentration response curves were not significantly different for the three drugs. When solutions of procaine and pentobarbital were mixed, the effect of the mixture was not significantly different from the effects of procaine and pentobarbital solutions, separately. Also, procaine shifted the concentration-response curve for pentobarbital in a manner expected for an additive interaction. When solutions of procaine and diethyl ether were mixed, the blockade by the mixture was significantly greater than the blockade by procaine and diethyl ether solutions, separately. Procaine shifted the concentration-response curve for diethyl ether in a manner that is greater than would be expected for an additive interaction. These results indicate that procaine and pentobarbital interact, additively, and that procaine potentiates the actions of diethyl ether. The potentiating interaction of procaine and diethyl ether suggests that the drugs have different mechanisms of action on the ganglion.

Animals↗
PubMed1980

Colorimetric determination of procaine hydrochloride in pharmaceutical preparations.

A new rapid, specific, and convenient colorimetric method for the determination of procaine hydrochloride in pharmaceutical preparations is described. This method is based on measurement of the intensity of the orange-red color developed when procaine hydrochloride is allowed to react with 1,2-naphthoquinone-4-sulfonic acid sodium salt in aqueous solution. Beer's law is followed over 6.0--20.0 micrograms/ml. The method was applied to the determination of procaine hydrochloride in procaine hydrochloride, procaine hydrochloride injection with or without epinephrine, penicillin G procaine, penicillin G procaine injection, and fortified procaine penicillin injection (BP). The results were comparable to those obtained by official procedures. Because of its simplicity, sensitivity, and accuracy, this method is particularly suited for routine analysis of official preparations of procaine hydrochloride.

Chemical Phenomena↗
PubMed1998

Effect of procaine hydrochloride on cyanide intoxication and its effect on neuronal calcium in mice.

Cyanide intoxication in mice can be antagonized by the local anesthetic, procaine HCI, either alone or in combination with sodium nitrite and/or sodium thiosulfate. Antitoxic potency, derived from LD50 values, was compared in groups of mice pretreated with sodium nitrite (43.9 mg/kg i.p.), sodium thiosulfate (1 g/kg i.p.), and procaine HCI (37.0 mg/kg i.p.) either alone or in various combinations. The results of present study indicated that procaine HCI provides a significant protection against the lethal effects of potassium cyanide. Dose-response studies revealed procaine hydrochloride pretreated 3 min before KCN, at doses of 18.48-73.9 mg/kg, produced significant elevation of KCN LD50, moreover it has a good dose-effect relationship, but its antidotal effect was weaker than sodium nitrite or sodium thiosulfate when they were administered alone. The protective effect of sodium nitrite and sodium thiosulfate was enhanced with procaine HCI. When procaine was administered in combination both with sodium nitrite and sodium thiosulfate, its protective effects were further enhanced. Its antitoxic potency is 6.22. The effects of procaine on antagonizing the cyanide-induced whole-brain total calcium increase were also studied. KCN (7 mg/kg i.p.) significantly increased whole-brain total calcium level from 28.37 +/- 0.75 to 48.05 +/- 1.06 mg/g dry wt within 30 min, which can be prevented by procaine pretreated 15 min before KCN. One of the possible mechanism of procaine on antagonizing cyanide toxicity seems, at least, related to its effect on inhibiting the cyanide-induced neuronal calcium increase and maintaining the homeostasis of neuronal calcium.

Anesthetics, Local↗
PubMed1984

Inhibitory effects of procaine on the contractile responses of the guinea-pig taenia caecum to acetylcholine, substance P and potassium chloride.

The effect of procaine on the contractile responses to acetylcholine, substance P and KCl was investigated using the isolated guinea-pig taenia caecum. In normal Tyrode solution (37 degrees C), procaine (10-100 mumol/l) caused a parallel shift to the right of only the dose-response curve of acetylcholine (pA2 value, 5.11). The pA2 value of procaine against acetylcholine was not significantly affected by increasing the Ca concentration in the bathing solution from 0.9 to 7.2 mmol/l. On the other hand, a high concentration of procaine (10 mmol/l) caused a transient contraction of the taenia caecum, but completely suppressed contractions to all concentrations of the agonists. In K-depolarized preparations, procaine (1-10 mmol/l) shifted the dose-response curve for the CaCl2-induced contraction to the right. Substance P (3 mumol/l)-induced contraction of the taenia caecum incubated with Ca-free EGTA (0.1 mmol/l) solution (20 degrees C) was markedly reduced by procaine (10 mmol/l). Using the single sucrose-gap technique, it was found that procaine (10 mmol/l) produced a membrane depolarization and increases in both amplitude and frequency of spontaneous spike discharge. These potential changes were still observed even after the procaine-induced contraction had disappeared. The spike discharges and contraction caused by procaine were abolished in the presence of a Ca-entry blocker, verapamil (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1982

Effect of procaine on potassium permeability of canine tracheal smooth muscle.

Procaine depolarized the cell membrane, and initiated oscillations and spike-like potentials in canine tracheal smooth muscle, at concentrations between 1 and 5 mM, while higher concentrations of this drug suppressed the spontaneous activities. Inhibitory effects of procaine on 86Rb-efflux were not evident in normal solution. In high K solution, procaine decreased the rate of 86Rb-efflux, in a dose dependent manner, and a Scatchard plot suggested two sites of action for procaine. The site with a higher affinity (KD = 0.26 mM) may directly regulate the K permeability and interact with procaine in a one to one manner. In high concentrations (greater than or equal to 10 mM), procaine interacted at another site and the tracheal smooth muscle which contracted in high K solution relaxed almost completely. Thus, the decrease in 86Rb-efflux by high concentrations of procaine may partly result from a decrease in intracellular Ca concentration. It is proposed that procaine has the dual effect by inhibiting the K conductance: (1) depolarization of cell membrane, (2) increase in membrane excitability. These actions would explain the spontaneous electrical activity induced by procaine in canine tracheal smooth muscle.

Animals↗
PubMed1993

Detecting localized proton currents in photophosphorylation by procaine inhibition of the transthylakoid pH-gradient.

The relationship between the transthylakoid pH-gradient, delta pH, and the velocity of photophosphorylation, Vp, in thylakoid membranes from spinach was investigated using the local anesthetic amine procaine as inhibitor of delta pH. When delta pH was driven by Photosystem (PS) II+I-dependent electron flow, passing through the cytochrome b6/f complex, inhibition by procaine was accompanied by an increase of ATP formation. It appeared that procaine allowed for values of Vp similar to those in controls (without procaine) at a significantly lower delta pH than in the controls. In contrast, when delta pH was driven by cyclic electron flow around PS I or by PS-II+I-dependent electron flow via a bypass around the cytochrome b6/f complex, or by PS II alone, procaine simultaneously caused an inhibition of delta pH and a decrease of ATP formation. Inhibition of delta pH by procaine did not induce an electrical membrane potential gradient that otherwise may have energetically compensated for the observed decline of delta pH. The electron flow capacity was unaffected by procaine. However, inhibition of delta pH did not significantly relax pH-dependent control of electron flux. Procaine accelerated ATP hydrolysis by pre-activated thylakoid ATPase to rates which were observed in the presence of uncouplers and had no direct effect on the activation state of the ATPase. The shift in the relationship between delta pH and Vp towards lower delta pH persisted in thermodynamic equilibrium between the phosphorylation potential and delta pH. The data indicated that the unconventional effect of procaine on photophosphorylation may be related to effects on proton translocation at the cytochrome b6/f complex and that a localized protonic coupling may occur between cytochrome b6/f and thylakoid-ATP-synthase complexes.

Chloroplasts↗
PubMed1998

Improvement of ischemic damage in gerbil hippocampal neurons by procaine.

Acute cerebral ischemia induces membrane depolarization in the neuron, thereby incurring the simultaneous influx of various ions such as Na+ and Ca2+. Since procaine possesses the ability to inhibit the release of Ca2+ from intracellular Ca2+ stores to the cytosol as well as the ability to block Na+ channels, the effects of procaine on ischemia were investigated in the present study in gerbils both in vivo and in vitro. The histologic outcome was evaluated 7 days after 3 min of transient forebrain ischemia by assessing delayed neuronal death in hippocampal CA1 pyramidal cells in animals administered procaine (0.2, 0.4, or 2 micromol) intracerebroventricularly 10 min before ischemia and in animals given saline. The changes in the direct-current potential shift in the hippocampal CA1 area were measured using an identical animal model. A hypoxia-induced intracellular Ca2+ increase was evaluated by in vitro microfluorometry in gerbil hippocampal slices, and the effects of procaine (10, 50, and 100 micromol/l) on the Ca2+ accumulation were examined. Additionally, the effect of procaine (100 micromol/l) in a Ca2+-free condition was investigated. The histologic outcome was improved and the onset of the ischemia-induced membrane depolarization was prolonged by the preischemic administration of procaine. The increase in the intracellular concentration of Ca2+ induced by the in vitro hypoxia was suppressed by the perfusion of procaine-containing mediums (50 and 100 micromol/l), regarding both the initiation and the extent of the increase. A hypoxia-induced intracellular Ca2+ elevation in the Ca2+-free condition was observed, and the perfusion with procaine (100 micromol/l) inhibited this elevation. Procaine helps protect neurons from ischemia by suppressing the direct-current potential shift and by inhibiting the release of Ca2+ from the intracellular Ca2+ stores, as well as by inhibiting the influx of Ca2+ from the extracellular space.

Anesthetics, Local↗
PubMed1999

Release of calcium and P-selectin from intraplatelet granules is hampered by procaine.

The inhibition of platelets by some local anaesthetics has been related to the modulation of platelet membrane lipid fluidity, and one of these compounds, procaine, has been proven to be particularly effective inhibitor. In the present study, we examined the effect of procaine on the mobilization of intracellular granule contents in isolated washed platelets. We revealed that the presence of 10 mg/ml procaine significantly hampered platelet release reaction, as demonstrated by the significant reduction in the expression of platelet P-selectin (CD62) on one hand, and significantly enhanced expression of GPIb alpha (CD42b) antigen on the other, following either 1 hour incubation of washed platelets at room temperature (%CD62: 37.1+/-6.8% of control incubated without procaine, p<<0.0001; %CD42b: 116.2+/-6.3% of control, p<0.0001) or activation of whole blood platelets with ADP, TRAP, or thrombin. Procaine, which acted as a rigidizer, significantly decreased platelet membrane fluidity (ESR h(+1)/h0 ratio of 5-DOXYL-Ste reduced down to 93.1+/-3.7% of control, p<0.001). In washed Fura-2-loaded platelets procaine not only brought about the significantly reduced Ca2+ release from intraplatelet storage pools after platelet stimulation with 15 micromol/l ADP (25.3+/-12.5% of control, p<0.001), but also it significantly increased the reduction in Ca2+ concentration upon the addition of Ca2+ chelator, EDTAK2 (48.9+/-13.5% vs. 40.9+/-12.1% of initial [Ca2+]i concentration, p(1,alpha)<0.025). Overall, procaine considerably reduced calcium mobilization from intraplatelet storage pools and Ca2+ efflux across platelet membrane. Based on these data, we suggest that the preventive effects of procaine on platelet release reaction and calcium mobilization might relate to the changes in the organization of membrane components embedded into a lipid bilayer, which are crucial in triggering of platelet release reaction. Procaine-mediated dislocations of some membrane components and/or distortion of lipid-protein interactions could generate a steric hindrance, which might interfere with platelet signal transduction, thus leading to impaired mobilization of Ca2+ and other components from intraplatelet storage pools.

Adenosine Diphosphate↗
PubMed2002

Stability-indicating HPLC assays for the determination of prilocaine and procaine drug combinations.

Stability-indicating, reversed phase high-performance liquid chromatographic (HPLC) methods have been developed for the determination of several procaine hydrochloride and prilocaine hydrochloride combinations. The separation and quantitation of epinephrine-prilocaine and epinephrine-procaine drug combinations were achieved on a phenyl column using a mobile phase of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt-acetonitrile at a flow rate of 1 ml x min(-1) and UV detection at 254 nm. The method showed linearity for the epinephrine and prilocaine hydrochloride mixture in the 0.25-2.5 and 8-200 micro g ml(-1) ranges, respectively. The intra- and inter-day relative standard deviations (RSDs) ranged from 0.26 to 2.05% and 0.04 to 0.61% for epinephrine and prilocaine hydrochloride, respectively. The epinephrine and procaine hydrochloride mixture yielded linear ranges of 0.25-2.0 and 5-100 micro g ml(-1) and intra- and inter-day RSDs ranged from 0.23 to 1.88% and 0.07 to 0.26% for epinephrine and procaine hydrochloride, respectively. The assays were shown to be suitable for measuring epinephrine-prilocaine and epinephrine-procaine combinations in their respective injection dosage forms. Stability-indicating HPLC assays were also developed for several other procaine drug combinations since their monographs are present in the USP 24; however, quantitation was not investigated since these combinations are not commercially available. A mobile phase consisting of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid-acetonitrile was utilized for the levonordefrin-tetracaine-procaine drug combination, while a mobile phase consisting of 70:30% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt-acetonitrile was utilized for the separation of levonordefrin-procaine-propoxycaine and norepinephrine-procaine-propoxycaine. All separations were achieved on a phenyl column at a flow rate of 1 ml x min(-1) and UV detection at 254 nm.

Anesthetics, Local↗
PubMed1989

Procaine rapidly inactivates acetylcholine receptors from Torpedo and competes with agonist for inhibition sites.

The relationship between the high-affinity procaine channel inhibition site (apparent dissociation constant Kp congruent to 200 microM) and the agonist self-inhibition site on acetylcholine receptors (AChRs) from Torpedo electroplaque was investigated by using rapid 86Rb+ quenched-flux assays at 4 degrees C in native AChR-rich vesicles on which 50-60% of ACh activation sites were blocked with alpha-bungarotoxin (alpha-BTX). In the presence of channel-activating acetylcholine (ACh) concentrations (10 microM-10 mM) alone, AChR undergoes one phase of inactivation (fast desensitization, rate = kd) in under a second. Addition of procaine produces two-phase inactivation similar to that seen with self-inhibiting (greater than 10 mM) ACh concentrations [Forman & Miller (1988) Biophys. J. 54, 149-158]--rapid inactivation (rate = kr) complete in 30-75 ms is followed by fast desensitization at the same kd observed without procaine. The dependence of kr on [procaine] is consistent with a bimolecular association between procaine and its AChR site with kon = 2.5 X 10(5) M-1 s-1, koff = 36 s-1, and Kp = 145 +/- 36 microM). Inhibition of AChR function by mixtures of procaine (up to 12Kp) plus self-inhibiting concentrations of ACh or suberyldicholine ([SubCh] up to 13 X the 50% self-inhibiting agonist concentration, KB) was studied by reducing the level of alpha-BTX block in vesicles. The apparent KB increased in the presence of procaine, and the apparent KP increased linearly with [SubCh], indicating mutually exclusive actions at a common AChR site. Our data support a mechanism where procaine binds preferentially to the open-channel AChR state, since no procaine-induced inactivation is observed without agonist and kr's dependence on [ACh] in the channel-activating range closely parallels that of 86Rb+ flux response to ACh.

Acetylcholine↗
PubMed1966

Competitive action of calcium and procaine on lobster axon. A study of the mechanism of action of certain local anesthetics.

Voltage clamp studies with the squid giant axon have shown that changes in the external calcium concentration (Frankenhaeuser and Hodgkin, 1957) shift the sodium and potassium conductance versus membrane potential curves along the potential axis. Taylor (1959) found that procaine acts primarily by reducing the sodium and, to a lesser extent, the potassium conductances. Both procaine and increased calcium also delay the turning on of the sodium conductance mechanism. Calcium and procaine have similar effects on lobster giant axon. In addition, we have observed that the magnitude of the response to procaine is influenced by the external calcium concentration. Increasing external calcium tends to reduce the effectiveness of procaine in decreasing sodium conductance. Conversely, procaine is more effective in reducing the membrane conductance if external calcium is decreased. The amplitude of the nerve action potential reflects these conductance changes in that, for example, reductions in amplitude resulting from the addition of procaine to the medium are partially restored by increasing external calcium, as was first noted by Aceves and Machne (1963). These phenomena suggest that calcium and procaine compete with one another with respect to their actions on the membrane conductance mechanism. The fact that procaine and its analogues compete with calcium for binding to phospholipids in vitro (Feinstein, 1964) suggests that the concept of competitive binding to phospholipids may provide a useful model for interpreting these data.

Animals↗
PubMed1988

The pH-dependent local anesthetic activity of diethylaminoethanol, a procaine metabolite.

To test whether the products of procaine hydrolysis have local anesthetic actions resembling those of procaine, the authors compared the ability of procaine and its metabolites diethylaminoethanol (DEAE) and para-aminobenzoic acid (PABA) to block compound action potentials in excised, desheathed frog and rat sciatic nerves. Studies were performed in solutions of impermeant buffers at pH 7.4 (corresponding to mammalian physiologic pH) and at pH 9.2 (close to the pKa of procaine and DEAE) to test for extracellular pH-dependent increases in drug permeation and potency. Both procaine and DEAE inhibited compound action potentials at pH 7.4 and 9.2 in a reversible and dose-dependent manner, and both were approximately ten-fold more potent at pH 9.2 than at pH 7.4, procaine inhibiting the action potential height by 50% at 0.15 mM (pH 9.2) and 1.1 mM (pH 7.4), DEAE at 4 mM (pH 9.2) and 70 mM (pH 7.4). In contrast, PABA at concentrations up to 25 mM and at either pH failed to inhibit compound action potentials, and did not modify the effects of DEAE when both drugs were given together. Procaine produced greater use-dependent block at the higher pH and at higher stimulation rates (100 Hz vs. 40 Hz); DEAE produced almost no use-dependent block. These observations suggest: 1) that DEAE might account for some of the neuropharmacologic activity of procaine in techniques that favor the accumulation of metabolites (such as those requiring large doses or prolonged infusions); and 2) that alkalinization of procaine and DEAE solutions appears to increase their potency for both resting and use-dependent block of action potentials.

4-Aminobenzoic Acid↗
PubMed1993

Respiratory alterations with intrapericardial procaine in the conscious rabbit.

1. Intrapericardial procaine, used to produce cardiac nerve blockade in both conscious and anaesthetized animals, has been reported to also produce changes in respiration. This study systematically investigated the effects of two doses of intrapericardial procaine on respiration in the conscious rabbit. 2. Rabbits were pre-instrumented with a chronic diaphragm electromyogram (dEMG) recording electrode and intrapericardial catheter. Arterial pressure, heart rate, dEMG and respiratory excursions (recorded with a pneumograph) were monitored in the conscious rabbit before and after intrapericardial and intravenous infusion of 2 and 5% procaine. Efficacy of cardiac nerve blockade was tested by intravenous infusion of phenyl biguanide. Arterial blood gases were determined at rest and during changes in respiration. 3. Following a low dose of intrapericardial procaine (12 mg), dEMG and respiratory excursions increased (65 +/- 13 and 76 +/- 32%, respectively) with no change in breathing frequency or arterial blood gases. Following a high dose of intrapericardial procaine (30 mg), four of six animals exhibited a similar response. However, four of the six rabbits also exhibited a second type of response pattern characterized by a further increase in respiratory efforts (430 +/- 336%), abolition of dEMG, and a mild hypoxaemia. 4. Intravenous infusion of a low dose of procaine was without effect, whereas intravenous infusion of a high dose of procaine produced minor behavioural responses. 5. In four additional anaesthetized rabbits, it was demonstrated that high doses of intrapericardial procaine anaesthetized the phrenic nerve to produce the observed alterations in respiration. 6. We conclude that if intrapericardial procaine is used to block cardiac nerves in conscious rabbits, it should be used in a low concentration and at the lowest possible total dose to avoid complications due to changes in respiration.

Absorption↗