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PubMed1998

Rapid actions of insulin on sensory nerve function.

The acute action of insulin on neurogenic flare was investigated using iontophoresis. Twenty-five patients with insulin-dependent diabetes mellitus (IDDM) and 25 age- and gender-matched controls were studied. Axon reflex vasodilatation was evoked by transdermal iontophoresis of acetylcholine (ACh) before and after skin treatment by the iontophoresis of insulin and measured using laser Doppler velocimetry. Axon reflex responses were reduced in IDDM patients compared with controls (p< 0.001) but were restored after the iontophoresis of insulin. Insulin iontophoresis had no effect on the size of the axon reflex response in control subjects (p > 0.05). This study confirms the reduction of the ACh-induced flare in human patients with IDDM and has demonstrated relatively rapid effects of insulin on this cutaneous neurogenic response.

Acetylcholine↗

PubMed1998

Venous ulcers: improved healing by iontophoretic administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide.

A study on the effects of iontophoretic administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide on the healing of venous stasis ulcers of the extremities was carried out on 66 patients. Two randomized groups of patients were compared, one receiving standard treatment plus iontophoresis of calcitonin gene-related peptide and vasoactive intestinal polypeptide, and the other receiving standard treatment plus placebo iontophoresis. Calcitonin gene-related peptide and vasoactive intestinal polypeptide were administered locally by iontophoresis for 20 min three times weekly for 12 weeks. To determine the effects of the two treatments, the percentage surface area of ulcer healed and the number of healed ulcers were compared after 2, 4, 6, 8, and 12 weeks of treatment. The results demonstrate that there were significant improvements of the healing process in the group treated with calcitonin gene-related peptide and vasoactive intestinal polypeptide when compared with placebo iontophoresis, and support the use of iontophoresis administration of calcitonin gene-related peptide and vasoactive intestinal polypeptide in the treatment of venous ulcers.

Aged↗

PubMed1978

Iontophoretic application of adenine arabinoside monophosphate to herpes simplex virus type 1-infected hairless mouse skin.

Several antiviral agents were applied topically or by iontophoresis to hairless mouse skin inoculated with herpes simplex virus type 1 (HSV-1), and the chemotherapeutic effectiveness was evaluated. Topical application of iododeoxyuridine, arabinoside A, and adenine arabinoside monophosphate (ara-AMP) moderately decreased the average lesion score, number of mice with paralysis, and number of mice dying in HSV-1-infected animals. Also, the mean survival time was moderately prolonged by topical application of those antiviral agents. When ara-AMP was applied by cathodal (-) iontophoresis to the HSV-1-infected skin, the average lesion score, number of mice with paralysis, and number of mice dying were greatly decreased. Furthermore, the mean survival time of mice was highly increased by cathodal (-) iontophoresis of ara-AMP. The therapeutic efficacy of ara-AMP iontophoresis was much superior to the topical application of iododeoxyuridine, arabinoside A, and ara-AMP. These data suggest that ara-AMP iontophoresis would be the method of choice for the management of HSV-1 skin lesions in hairless mice.

Animals↗

PubMed1988

Iontophoretic application of tobramycin to uninfected and Pseudomonas aeruginosa-infected rabbit corneas.

Pseudomonas aeruginosa keratitis was induced in rabbits to study the effects of corneal infection on the delivery of tobramycin by iontophoresis. Some rabbits were treated by use of an eye cup with no current as a control for iontophoresis, and others were treated with fortified drops (1.36%) delivered topically for comparison with results of earlier studies. One hour after treatment with tobramycin, the concentration of drug in the infected corneas was compared with that achieved in mock-infected and uninfected eyes. Iontophoresis of 25 mg of tobramycin per ml at 0.8 mA for 10 min delivered significantly more drug (P = 0.0001) to corneal tissue than did drops or use of an eye cup without current in P. aeruginosa-infected eyes mock-infected eyes, or uninfected eyes. Tobramycin concentrations in the infected corneas (605.9 micrograms/g) were not significantly different (P = 0.815) from the concentrations in mock-infected eyes (641.4 micrograms/g), but were lower (P = 0.007) than those obtained by iontophoresis in uninfected corneas (853.6 micrograms/g). Use of an eye cup without current delivered tobramycin equally to infected, mock-infected, and normal eyes, i.e., 176.5, 171.0, and 163.1 micrograms/g, respectively (P greater than 0.709). Tobramycin delivered by use of fortified drops delivered topically was detectable in mock-infected corneas (20 micrograms/g) and P. aeruginosa-infected corneas (6.0 micrograms/g). These results suggest that iontophoresis has value as an ocular drug delivery system and that an eye cup could also be useful in a therapeutic regimen for ocular infections.

Animals↗

PubMed1993

Alpha 2-adrenoceptor-mediated inhibition of bulbospinal barosensitive cells of rat rostral medulla.

Bulbospinal barosensitive neurons of the rostral ventrolateral medulla (RVLM cells; presumed sympathetic vasomotor premotor neurons) were recorded with iontophoretic electrodes in urethan-anesthetized rats. The majority of these cells were insensitive to intravenous clonidine (Clo; up to 20 micrograms/kg) and insensitive to iontophoretically applied Clo or alpha-methylnorepinephrine (alpha-MNE). These cells (n = 47 of 76) had a spinal conduction velocity of 4.1 +/- 0.2 m/s and a mean firing rate of 20 +/- 1 spikes/s. A second population (n = 29) was powerfully inhibited by intravenous Clo (5-10 micrograms/kg, activity decreased by 83 +/- 11%), iontophoretically applied Clo (decreased by 51 +/- 7%), and iontophoresis of alpha-MNE (decreased by 69 +/- 3%). These cells had a slower conduction velocity (2.0 +/- 0.3 m/s) and a much slower discharge rate (6 +/- 1 spikes/s). Both populations were pulse synchronous at resting arterial pressure. The inhibitory effects produced by iontophoresis of alpha-MNE or Clo were reduced to the same degree (86-98%) by iontophoresis of idazoxan (an alpha 2-adrenergic antagonist with imidazoline structure) and by iontophoresis of piperoxan (65-77%, a nonimidazoline alpha 2-antagonist). The inhibition of RVLM cells by intravenous Clo was reversed by iontophoresis of idazoxan and by intravenous injection of yohimbine (nonimidazoline alpha 2-antagonists). These data suggest that 1) intravenous Clo only inhibits a subpopulation of RVLM sympathetic premotoneurons, possibly the C1 adrenergic cells, 2) this effect of Clo is due to activation of alpha 2-adrenergic receptors rather than nonadrenergic imidazoline binding sites, and 3) these alpha 2-receptors are located on or close to the Clo-sensitive cells and may be continuously activated by endogenously released catecholamines.

Adrenergic alpha-Antagonists↗

PubMed2004

Influence of vehicle resistance on transdermal iontophoretic delivery of acetylcholine and sodium nitroprusside in humans.

Iontophoresis is a valuable method of noninvasive drug delivery for assessment of skin microvascular function, but it is important to consider and minimize its potential nonspecific electrical effects on blood flow. The use of sodium chloride (NaCl) instead of water as the iontophoresis vehicle has been reported to reduce these effects because it has a lower electrical resistance. However, this argument may not be valid when an agonist is added to the vehicle because its resistance will be changed. The aim of our study was to determine whether there is a difference in resistance between water and NaCl when used as vehicles for iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Four cumulative doses of each drug, dissolved in either water or NaCl, were delivered via iontophoresis to the forearm skin of 14 healthy volunteers. We measured the resulting blood flow responses by using laser-Doppler imaging and the voltage across the electrodes for each delivery as an index of resistance. For ACh and SNP, there were no significant differences between the voltages measured when either water or NaCl was used as the vehicle. However, the blood flow responses to both agonists were significantly lower with NaCl (ACh: 25% lower, P < 0.001; SNP: 15% lower, P = 0.019). The use of NaCl is therefore unlikely to decrease any nonspecific electrical effects, and it may in fact reduce the effective dose of drug delivered. Deionized water is a better iontophoresis vehicle for the assessment of microvascular function in skin when using ACh and SNP.

Acetylcholine↗

PubMed1998

Synaptically evoked dendritic action potentials in rat neocortical pyramidal neurons.

In a previous study iontophoresis of glutamate on the apical dendrite of layer 5 pyramidal neurons from rat neocortex was used to identify sites at which dendritic depolarization evoked small, prolonged Ca2+ spikes and/or low-threshold Na+ spikes recorded by an intracellular microelectrode in the soma. These spikes were identified as originating in the dendrite. Here we evoke similar dendritic responses by electrical stimulation of presynaptic elements near the tip of the iontophoretic electrode with the use of a second extracellular electrode. In 9 of 12 recorded cells, electrically evoked excitatory postsynaptic potentials (EPSPs) above a minimum size triggered all-or-none postsynaptic responses similar to those evoked by dendritic glutamate iontophoresis at the same site. Both the synaptically evoked and the iontophoretically evoked depolarizations were abolished reversibly by blockade of glutamate receptors. In all recorded cells, the combination of iontophoresis and an EPSP, each of which was subthreshold for the dendritic spike when given alone, evoked a dendritic spike similar to that evoked by a sufficiently large iontophoresis. In one cell tested, dendritic spikes could be evoked by the summation of two independent subthreshold EPSPs evoked by stimulation at two different locations. We conclude that the dendritic spikes are not unique to the use of glutamate iontophoresis because similar spikes can be evoked by EPSPs. We discuss the implications of these results for synaptic integration and for the interpretation of recorded synaptic potentials.

2-Amino-5-phosphonovalerate↗

PubMed1994

5-HT1A receptors mediate the effect of the bulbospinal serotonin system on spinal dorsal horn nociceptive neurons.

The present study examined whether the effect of stimulation of the nucleus raphe magnus (NRM) is mediated by spinal cord dorsal horn serotonin1A (5-HT1A) receptors in the rat. This hypothesis predicts that nociceptive dorsal horn units inhibited by NRM stimulation or iontophoretic 5-HT application would also be inhibited by iontophoresis of the selective 5-HT1A agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone. A total of 78 dorsal horn wide-dynamic-range neurons were recorded. Overall, 62% of the cells tested (48/78) were responsive to electrical stimulation of the NRM with the predominant response being inhibitory (38/48; 79%). Fifty-eight cells were tested for their response to both NRM stimulation and 8-OH-DPAT iontophoresis: 20/58 cells were inhibited by NRM stimulation and 50% of the cells inhibited by NRM stimulation were also inhibited by 8-OH-DPAT. Fifty-two cells were tested for their response to both NRM stimulation and buspirone iontophoresis: 14/52 cells were inhibited by NRM stimulation with 9/14 similarly inhibited by buspirone. To examine whether exogenously applied serotonin produced an effect through 5-HT1A receptors, the effect of both 5-HT and 8-OH-DPAT iontophoresis was tested on 57 dorsal horn neurons. The majority of cells (25/57) were inhibited by 5-HT application; 15/25 were similarly inhibited by 8-OH-DPAT. The response of 48 dorsal horn cells to 5-HT and buspirone iontophoresis was compared. Forty-four percent (21/48) of the cells were inhibited by 5-HT; 16/21 were also inhibited by buspirone.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2004

Central control of electric signaling behavior in the mormyrid Brienomyrus brachyistius: segregation of behavior-specific inputs and the role of modifiable recurrent inhibition.

Like all mormyrid fish, Brienomyrus brachyistius produces an electric organ discharge (EOD) with a constant waveform and variable sequence of pulse intervals (SPI). Periodic bursts fall into two display categories termed 'scallops' and 'accelerations', with a third category termed 'rasps' that appears to combine the two. The medullary EOD command nucleus (CN) receives excitatory input from the midbrain precommand nucleus (PCN) and the thalamic dorsal posterior nucleus (DP), both of which are regulated by a recurrent inhibitory projection from the ventroposterior nucleus of the torus semicircularis (VP). We tested the following hypotheses: (1) PCN and DP are responsible for generating different burst types (scallops and accelerations, respectively), (2) differences in the strength of recurrent inhibition are related to physiological differences between PCN and DP and (3) recurrent inhibition regulates the resting electromotor rhythm, while disinhibition releases PCN and DP, allowing them to generate bursts. Iontophoresis of the excitatory neurotransmitter L-glutamate (L-Glu) into DP led to acceleration-like output patterns, while in PCN it led to scallop-like output patterns. Iontophoresis of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA) into DP and PCN led to an elongation of intervals, as did iontophoresis of L-Glu into VP. Iontophoresis of the GABA(A) receptor blocker bicuculline methiodide (BMI) into DP and PCN induced repetitive bursting behavior and eliminated differences in the effects of L-Glu iontophoresis in the two nuclei. These results support our three hypotheses, suggesting that production of different communication behaviors may be regulated by spatially distinct groups of neurons, and recurrent inhibition and disinhibition may play an active role in driving and shaping such behaviors.

Animal Communication↗

PubMed2003

Intradermal delivery of antisense oligonucleotides by the pulse depolarization iontophoretic system.

The intradermal delivery of an antisense oligonucleotide was examined by iontophoresis. In this experiment, the antisense sequence of [(32)P]-labeled phosphodiester oligonucleotide ([(32)P]D-oligo, 18-mer) hybridizing to mouse interleukin 10 (IL-10) mRNA was used as a model D-oligo. In in vitro iontophoretic experiments, isolated hairless mouse skin was used with a horizontal diffusion cell. The enhancing effect of pulse depolarization (PDP) iontophoresis on the [(32)P]D-oligo permeation through the skin was better, and the skin irritation was less, than those of constant direct current (CDC) iontophoresis. The apparent fluxes of [(32)P]D-oligo were enhanced with the increasing current densities and [(32)P]D-oligo concentrations in the donor solution, whereas the enhanced flux decreased with the increasing NaCl concentrations in the donor solution. An optimum electric current was observed for the intradermal delivery of [(32)P]D-oligo, and intact [(32)P]D-oligo was detected within the skin after iontophoresis for 6 h. These results suggest that PDP iontophoresis may be useful for the intradermal delivery of antisense oligonucleotides.

Animals↗

PubMed1985

HSV-1 quantitation from rabbit neural tissues after epinephrine-induced reactivation.

Epinephrine iontophoresis into the eye can induce ocular herpes simplex virus type-1 (HSV-1) shedding with a high frequency from latently infected rabbits. The present study was designed to qualify and quantify infectious HSV-1 from neural tissues of latently infected rabbits after ocular epinephrine iontophoresis. Epinephrine iontophoresis was performed daily for 3 consecutive days on selected days during 220-227 days postinoculation. The induced ocular shedding was detected in the tear film with a frequency of 83% (10/12) within 72 hr after the initial iontophoresis. The rabbits were killed 24 hr after the last iontophoretic treatment, and the corneas and neural tissues were homogenized immediately. The cell-free supernatants were inoculated on primary rabbit kidney cell monolayers for qualitative assays of infectious virus and later titrated on CV-1 monolayers. The frequencies of the recovery of infectious HSV-1 from the cell-free homogenates were 0% of the corneas (0/12), 83% (10/12) from the superior cervical ganglion (SCG), 100% (12/12) from the trigeminal ganglion (TG), 42% (5/12) from the ophthalmic branch of the trigeminal nerve (TN), 8% (1/12) from the root entry zone of the trigeminal nerve into the brain-stem (REZ), and 0% (0/12) from the cerebellum. The authors conclude that epinephrine iontophoresis can reactivate the latent HSV-1 in neural tissues and infectious virus can be quantified from the cell-free homogenates. To the best of our knowledge, this is the first report to quantify HSV-1 with a high frequency from neural tissues following induced reactivation.

Animals↗

PubMed1979

Effect of iontophoretic and topical application of antiviral agents in treatment of experimental HSV-1 keratitis in rabbits.

Cathodal (-) iontophoresis of 9-beta-D-arabinofuranosyl-adenine 5'-monophosphate (vidarabine monophosphate; Ara-AMP) was performed once daily for 3 days for the treatment of experimental herpes simplex virus type 1 (HSV-1) keratitis in rabbit eyes, and the therapeutic efficacy was compared with that of topical treatment of Ara-AMP and idoxuridine (IDU) administered five times daily for 4 days. With the treatment initiated 24 hr after viral inoculation, Ara-AMP cathodal iontophoresis resulted in significant suppression of epithelial and anterior segment disease processes. Topical IDU (0.5%) or Ara-AMP (10%) also significantly improved the disease process when compared to the placebo-treated group; however, iontophoresis of Ara-AMP resulted in a more marked improvement. Slit-lamp examination indicated that iontophoresis did not cause any observable pathologic changes in corneal epithelium, stroma, conjunctiva, or iris of rabbit eyes. This experiment suggests that iontophoresis of Ara-AMP is a safe and effective approach for preventing the development of herpes simplex keratitis in rabbits.

Administration, Topical↗

PubMed2002

Electrically modulated transdermal delivery of fentanyl.

PURPOSE: Test to determine if iontophoresis and electroporation, alone or in combination, can be used for rapid and modulated delivery of fentanyl. METHODS: Fentanyl citrate (5 mg/ml) dissolved in pH 4.0 citrate buffer was delivered in vitro across human epidermis. For iontophoresis. a current of 0.5 mA/cm2 was applied for 5 h, using silver/silver chloride electrodes. Electroporation protocol consisted of applying 15 exponential pulses of 500V (applied voltage) and 200 msec duration at the rate of 1 pulse per minute at time zero and, in some cases, repeating at 1.5 and 2.5 h. RESULTS: There was no measurable permeation of fentanyl through human epidermis under passive conditions. A significant flux (about 80 microg/cm2-hr) was achieved using iontophoresis and decreased once the current was turned off. A 4-fold higher flux and shorter lag time was observed with electroporation as compared to iontophoresis. The flux was found to recover quickly (within 1 h) following pulsing. Modulation of transdermal delivery of fentanyl was demonstrated by both iontophoresis and electroporation. CONCLUSIONS: Electrically assisted transdermal delivery of fentanyl significantly increased transport compared to passive delivery. Also, rapid and modulated delivery was shown to be feasible by programming the electrical parameters.

Administration, Cutaneous↗

PubMed1990

Effects of glycine and GABA on bulbar respiratory neurons of cat.

1. Bulbar respiratory neurons of unanesthetized, decerebrate cats were impaled with the center pipette of a compound, coaxial microelectrode. This electrode allowed intracellular recording of membrane potential (MP) through the central pipette and extracellular iontophoresis of glycine or gamma-aminobutyric acid (GABA) from micropipettes encircling the center pipette with their tips recessed 20-40 microns from the tip of the center pipette. 2. Seventy-seven studies were carried out on 32 inspiratory and 28 postinspiratory neurons with the use of brief pulses (0.3-0.5 s) or long pulses (3-10 s) spanning one or more respiratory cycles. In both neuronal types, GABA and glycine decreased spike frequency, synaptic "noise," respiratory fluctuations of MP, and "input" resistance in a dose-related fashion. 3. In most cases, the membrane was hyperpolarized by the amino acid. The reverse response (depolarization) was observed when the membrane had been hyperpolarized by current clamp. This reversal from hyperpolarization to depolarization occurred at a MP of -81 +/- 2.3 mV (mean +/- SE, n = 7) for glycine and -81 +/- 1.6 (n = 6) for GABA. 4. After intracellular iontophoresis of chloride ions, application of GABA and glycine depolarized the membrane. 5. During relatively long (3-10 s) periods of iontophoresis of glycine or GABA, the effects on MP and input resistance waned. In some cases (23%), the amino acid depolarized the membrane at the most hyperpolarizated portion of the MP trajectory. This was never observed with brief iontophoretic pulses. Such effects of long duration iontophoresis may reflect changes in membrane properties secondary to the primary action of the amino acid on the membrane of the impaled neuron or indirect synaptic actions via changes in discharge of neighboring neurons. 6. Extracellular iontophoresis of a GABA uptake inhibitor, nipecotic acid, potentiated the effects of GABA. 7. Extracellular application of tetrodotoxin appeared to act pre- and postsynaptically to reduce respiratory fluctuations in membrane potential and to increase input resistance without altering the effects of iontophoresed glycine and GABA, suggesting that the amino acids act on postsynaptic membrane receptors not linked to fast sodium channels.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1984

Experimental studies on different thresholds for epileptiform activity.

This investigation was carried out to clarify the mechanisms for production of different seizure threshold. To study this problem changes of a single cell activity were examined by means of penicillin iontophoretical application to a single cell of both low seizure threshold hippocampus and the high seizure threshold olfactory bulb, and also topical application to the surface of hippocampus and olfactory bulb. Penicillin was applied iontophoretically using five barrel glass micropipettes. Extracellular recordings from 58 hippocampal pyramidal cells and 68 olfactory bulb mitral cells were analyzed. Penicillin increased the firing rate in most of both hippocampal pyramidal and olfactory bulb mitral cells. This suggests that penicillin finally had an excitatory effect on both cells. The results from the experiments of intermittent and continuous GABA application on a cell during penicillin iontophoresis revealed that GABA inhibitory action was reduced by penicillin in both cells. A progressively shortened duration of the post-discharge inhibition during penicillin iontophoresis also suggested that penicillin may reflect a decrease of GABA inhibitory action. No obvious seizure activity and/or no change of firing pattern were observed even after long penicillin iontophoresis. There was no significant different responses to penicillin iontophoresis in the hippocampus and the olfactory bulb single cell. Extracellular activity from 64 hippocampal pyramidal cells and 32 olfactory bulb mitral cells was recorded. The effects of penicillin topical application on single cell function were examined. From hippocampus surface, paroxysmal activity begun to appear within 6 min after topical application, and became more regular and stereotyped in form. The firing rate initially decreased in the majority of cells, with no increase prior to interictal or ictal events. The unit responses to both intermittent and continuous GABA iontophoresis was suppression in unit firing incidence, except for the burst patterns associated with the surface interictal or ictal discharges. Post-discharge inhibition was not significantly different either before or after the onset of the surface interictal discharges. These results indicate the firing rate and inhibitory function of the hippocampal pyramidal cells were not significantly changed during and following the development of interictal and/or ictal epileptiform activity. Olfactory bulb surface activity was not significantly changed and no epileptiform activity was observed even several hours after topical penicillin application.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery.

Three factors are of primary importance in determining the iontophoretic flux of a charged solute: the electrochemical potential gradient across the skin, an increase in skin permeability to passive transport due to iontophoresis (loosely defined as skin damage), and a current-induced water flux. The latter two factors can also affect the transport of uncharged solutes during iontophoresis. A method of correcting for the skin damage effect is introduced. The contributions of the water transport effect relative to that of the applied voltage drop for charged solutes is estimated. It is shown that the water transport contribution is generally lower than the contribution due to the applied voltage drop. The observed iontophonetic flux of the enhancement factors due to the applied voltage drop alone are compared with the theoretical predictions based on the constant field assumption. It is shown that the theoretical predictions are higher than the experimental observations. This work also examines, for the first time, a synergism of iontophoresis and pretreatment with a chemical penetration enhancer as a means for delivering high molecular weight polypeptides. It is shown that a 2-h pretreatment with absolute ethanol followed by iontophoresis dramatically increases the permeability coefficient of insulin through human skin.

Administration, Cutaneous↗

PubMed1979

Correlated effects of acetylcholine and cyclic guanosine monophosphate on membrane properties of mammalian neocortical neurons.

The effects of successive extracellular iontophoresis of acetylcholine (ACh) and atropine, and intracellular hyperpolarizing iontophoresis of cyclic GMP (cGMP) were studied in single neurons of the coronal-pericruciate cortex of awake cats. (a) Fifty-seven percent of the neurons that were tested responded to ACh with an increase in neuronal input resistance (Rm) and 50% responded to ACh with an increase in firing rate; 65% responded to cGMP with an increase in Rm and 60% responded to cGMP with an increase in firing rate. (b) After application of atropine, increases in Rm and firing rate associated with iontophoresis of ACh failed to recur. (c) Persistent increases in Rm following application of ACh accompanied by current-induced neuronal discharge were not diminished by subsequent application of atropine. (d) Atropine did not prevent increases in Rm and firing rate associated with intracellular iontophoresis of cGMP. (e) All cells tested with both ACh and cGMP that were shown initially to respond to extracellular ACh with increases in Rm were later shown to have comparable responses to cGMP.

Acetylcholine↗

PubMed1992

Iontophoretically enhanced transdermal delivery of an ACE inhibitor in induced hypertensive rabbits: preliminary report.

Both conventional direct current (DC) and pulsed-mode DC constant-current iontophoresis were used to investigate enhanced transdermal delivery of the angiotensin-converting enzyme (ACE) inhibitor captopril to rabbits with acutely induced hypertension. Passive transdermal captopril administration and pulsed DC constant-current iontophoresis of the vehicle were studied as control experimentation. Mean arterial pressure (MAP) was not significantly (p > 0.05) altered following passive transdermal delivery of captopril (n = 4) or after iontophoretic delivery of the vehicle alone (n = 4). Pressure reduction was evident within 10 minutes of iontophoretic enhancement of transdermal captopril delivery. DC mode constant-current (n = 4) iontophoretic transdermal captopril administration caused MAP to fall by 21% from a mean hypertensive level of 66 +/- 5 mmHg to a mean post-treatment level of 52 +/- 6 mmHg (p < 0.05) within 60 minutes. Pulsed DC mode constant-current (n = 4) iontophoresis of captopril caused mean MAP to fall on average by 27% from 62 +/- 6 to 45 +/- 5 mmHg (p < 0.05), also within 60 minutes. This paper provides the first report on the enhanced efficiency during iontophoretic delivery of an ACE inhibitor. We have concluded that both modes of constant-current iontophoresis of captopril offer a safe and effective means of pressure reduction in rabbits with induced hypertension and that there is no significant difference in efficacy between the two forms of enhanced delivery. These results have potential applications for enhanced transdermal delivery of ACE inhibitors in humans.

Administration, Cutaneous↗