Pioglitazone.

Pioglitazone is a thiazolidinedione antidiabetic with actions similar to those of rosiglitazone. It is used in the management of type 2 diabetes mellitus and is prepared by reducing 5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzilidene]-2,4-thiazolidinedione with sodium borohydride in the presence of a cobalt ion and dimethyl glyoxime. Ultraviolet spectroscopy shows maximum absorption at 270nm. Infrared spectroscopy shows principal peaks at wave numbers 3082, 2964, 1736, 1690, 1472, 1331, 1254, 1040, 841, 728cm(-1) (KBr disk). The determination method by high-performance liquid chromatography was linear over the range of 25-1500ng/mL of pioglitazone in plasma (r(2)>0.999). The within- and between-day precision values were in the range of 2.4-6.8%. The limit of quantitation of the method was 25ng/mL. It is well absorbed with a mean absolute bioavailability of 83% and reaching maximum concentrations in around 1.5h. It is metabolized by the hepatic cytochrome P450 enzyme system. Following oral administration, approximately 15-30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces.

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Characteristics of new composite- and classical potentiometric sensors for the determination of pioglitazone in some pharmaceutical formulations.

The construction and electrochemical response characteristics of poly(vinyl chloride) membrane sensors for pioglitazone HCl (PG) are described. The sensing membranes incorporate ion association complexes of pioglitazone cation and sodium tetraphenylborate (NaTPB) (sensor 1) or phosphomolybdic acid (PMA) (sensor 2) or phosphotungstic acid (PTA) (sensor 3) as electroactive materials. The sensors display a fast, stable and near-Nernstian response over a relative wide pioglitazone concentration range (1x10(-2) to 10(-6) M), with cationic slopes of 55.0+/-0.5, 58.0+/-0.5 and 53.0+/-0.5 mV per concentration decade over a pH range of 1.0-5.0. The sensors show good discrimination of pioglitazone from several inorganic and organic compounds. The direct determination of 2.5-3900.0 microg/ml of pioglitazone show an average recovery of 98.5, 99.0 and 98.4% and a mean relative standard deviation of 1.6, 1.5 and 1.7% at 100.0 microg/ml for sensors 1, 2 and 3, respectively. The proposed sensors have been applied for direct determination of pioglitazone in some pharmaceutical preparations. The results obtained by determination of pioglitazone in tablets using the proposed sensors are comparable favorably with those obtained using the HPLC method. The sensors have been used as indicator electrodes for potentiometric titration of pioglitazone.

NAN-190, a possible specific antagonist for methamphetamine.

Effect of NAN-190, a selective 5-HT(1A) receptor antagonist, on methamphetamine-induced locomotor activity, anorexia, analgesia, and hyperthermia was investigated in male mice. Methamphetamine (1.5 mg/kg, i.p) produced a significant increase in locomotor activity, which was significantly antagonized by NAN-190 at a dose of 4 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone. Methamphetamine (2 mg/kg, i.p) produced a significant decrease in food intake of mice, which were deprived of food during the previous 24h. This anorectic activity of methamphetamine was significantly antagonized by NAN-190 at a dose of 2 mg/kg, i.p. NAN-190 did not alter the food intake of mice when it was administered alone. Methamphetamine (2 mg/kg, i.p) also produced a significant increase in body temperature of mice, which was significantly antagonized by NAN-190 at a dose of 0.5 mg/kg, i.p. NAN-190 did not alter the body temperature of mice when it was administered alone. In the writhing test, methamphetamine (1 mg/kg, i.p) produced a significant antinociceptive effect in mice. This was significantly antagonized by NAN-190 at a dose of 1 mg/kg, i.p. NAN-190 did not alter the antinociceptive activity of mice when it was administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the above-studied activities of methamphetamine in mice. This role is possibly mediated through direct stimulation of the 5-HT(1A) receptor subtype. All of the above-studied activities of methamphetamine were antagonized by NAN-190, which may indicate that NAN-190 is a possible antagonist for methamphetamine.

Ondansetron, a selective 5-HT3 antagonist, antagonizes methamphetamine-induced anorexia in mice.

Effects of some selective serotonergic (5-HT) antagonists on methamphetamine-induced anorexia were investigated in male mice. The least possible dose of methamphetamine alone that caused significant anorectic activity was 11 micromolkg(-1), i.p. (2 mgkg(-1)). Various doses of some selective serotonergic receptor antagonists were administered half an hour before the above mentioned dose of methamphetamine. Methiothepin potentiated, whereas NAN-190, methysergide, mianserin and ondansetron antagonized methamphetamine-induced anorectic activity. The least possible doses of these antagonists which modified methamphetamine-induced anorexia were as follows: methiothepin (1.1 micromolkg(-1), i.p.), NAN-190 (4.2 micromolkg(-1), i.p.), methysergide (2.1 micromolkg(-1), i.p.), mianserin (3.3 micromolkg(-1), i.p.) and ondansetron (0.003 micromolkg(-1), i.p.). The serotonergic antagonists at the above mentioned doses did not modify the food intake of animals not treated with methamphetamine, except for methiothepin, which produced a significant reduction, and mianserin, which produced a significant increase in food intake. The results of the present study indicated that the anorectic activity induced by methamphetamine is related to the interactions of methamphetamine with 5-HT receptor. Since a very small dose (0.003 micromolkg(-1)) of ondansetron (the 5-HT(3) antagonist), as compared with the other antagonists used in this study, antagonized the anorexia induced by methamphetamine, the 5-HT(3) receptor is likely to be the site for this interaction.

Voltammetric study of danazol and its determination in capsules and spiked biological fluids.

The voltammetric behaviour of danazol DZ (antigonadotropin) was studied using cyclic voltammetry, direct current, differential pulse polarography (DPP) and alternating current polarography. Danazol exhibited irreversible cathodic waves over the pH range of 1-5 in Britton Robinson buffers. At pH 1 (the analytical pH), a well-defined wave with E1/2 of -1.04 V versus Ag/AgCl reference electrode was obtained. The diffusion current constant (Id) was 4.8+/-0.14 microA.L.m mole(-1) and the current-concentration plot was rectilinear over the range from 5 x 10(-6) to 1 x 10(-4) M with correlation coefficient (n = 11) of 0.995. The calculated detection limit was 1 x 10(-6) M using the DPP mode. The wave was characterized as being irreversible, diffusion-controlled although adsorption phenomenon played a limited role in the electrode process. The proposed method was applied to commercial capsules and the average percentage recovery was in agreement with that obtained by the official USP method. The method was extended to the in vitro determination of DZ in spiked human urine and plasma samples, the percentage recoveries were 96+/-4 and 97+/-5, respectively. A proposal of the electrode reaction was postulated.

Involvement of some 5-HT receptors in methamphetamine-induced locomotor activity in mice.

Effects of some selective 5-HT antagonists on methamphetamine-induced locomotor activity were investigated in male mice in order to study whether this effect of methamphetamine is selectively or at least partially, induced through stimulation of a specific serotonin receptor subtype. Methamphetamine (1.5 mg/kg, IP) produced a significant increase in locomotor activity. Methamphetamine-induced hyperactivity by the above mentioned dose was significantly antagonized by NAN-190 ( 5-HT(1A) antagonist) at a dose of 4 mg/kg, IP, methiothepin (5-HT(1B/1D) antagonist) at a dose of 0.1mg/kg, IP or mianserin ( 5-HT(2C) antagonist) at a dose of 8 mg/kg, IP. On the other hand, methysergide ( 5-HT(2A/2B) antagonist) at a dose of 1mg/kg, IP or ondansetron ( 5-HT(3) antagonist) at a dose of 0.5mg/kg, IP potentiated the methamphetamine-induced hyperactivity. None of the above mentioned doses of 5-HT antagonists altered the spontaneous activity of mice when administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the locomotor stimulant activity of methamphetamine in mice. This role is possibly mediated through direct stimulation of some 5-HT receptor subtypes. Stimulation by methamphetamine of 5-HT(1A), 5-HT(1B/1D) and/or 5-HT(2C) receptor subtypes may result in hyperactivity, whereas stimulation by methamphetamine of 5-HT(2A/2B) and/or 5-HT(3) receptor subtypes may result in decreased activity.

Potentiation of diclofenac-induced anti-inflammatory response by aminoguanidine in carrageenan-induced acute inflammation in rats: the role of nitric oxide.

OBJECTIVE: To investigate whether aminoguanidine (AG) treatment enhances the anti-inflammatory effect of diclofenac in an acute inflammation model in rats. MATERIAL AND METHODS: In 48 rats carrageenan-induced paw edema was used as an acute inflammation model. Inflammatory activity was assessed at 1.5, 3 and 6 h after sub-planter injection of carrageenan (0.1 ml of a 1% solution in 0.85% saline). The anti-inflammatory effect of diclofenac (25 mg/kg, i.p.) was studied in comparison to that of the selective inducible nitric oxide synthase (iNOS) inhibitor, AG, and of nitric oxide donor, sodium nitroprusside (SNP). RESULTS: AG, failed to inhibit inflammation during the first 3 h following carrageenan administration, but caused a slight, although statistically insignificant inhibition at 6 h. Diclofenac significantly reduced the carrageenan-induced edema in rat paw at all the time points studied. Administration of diclofenac after AG pretreatment caused significant (P < 0.001) reduction in edema that was double that of diclofenac alone 6 h after carrageenan injection. Administration of SNP as a single dose after AG pretreatment prevented any potentiation of anti-inflammatory response that was observed in the case of AG combined with diclofenac treatment. CONCLUSION: These results show that AG markedly potentiates the anti-inflammatory activity of diclofenac at 6 h and this potentiation effect is nitric oxide-dependent.

Voltammetric determination of isradipine in dosage forms and spiked human plasma and urine.

The voltammetric behavior of isradipine was studied using direct current (DC(t)), differential-pulse (DPP) and alternating current (AC(t)) polarography. Isradipine exhibited well-defined cathodic waves over the whole pH range in Britton-Robinson buffer (BRb). At pH 5, the analytical pH, the diffusion-current constant (Id) was 8.27+/-0.52. The current-concentration plots were rectilinear over the range 1-20 and 0.1-18 microg/ml using the DC(t) and DPP modes, respectively, with minimum detectability of 0.01 microg/ml (2.7 x 10(-8) M) using the latter technique. The current has been characterized as being diffusion-controlled, although adsorption phenomenon played a limited role in the electrode process. The proposed method was applied to commercial tablets and capsules. The percentage recoveries were in good agreement with those given by the manufacturer. The method was further extended to the in-vitro determination of the drug in spiked human urine and plasma, the percentage recoveries were (n = 4) 100.12+/-1.42 and 103.88+/-5.13, respectively. The number of electrons involved in the reduction process was accomplished and a proposal of the electrode reaction was presented.

Spectrofluorometric determination of nimodipine in dosage forms and human urine.

A simple sensitive and specific spectrofluorometric method was developed for the determination of nimodipine (NDP) in pharmaceutical preparations and human urine. The method is based on reduction of nimodipine with Zn/HCl and measuring the obtained fluorescence at 425 nm after excitation at 360 nm. The factors affecting the development of the fluorophore and its stability were studied and optimized. The effect of some surfactants such as beta-cyclodextrin (betaCD), carboxymethylcelullose (CMC), sodium dodecyl sulphate (SDS) and Triton X-100, on the fluorescence intensity was studied. The fluorescence intensity-concentration plot is rectilinear over the range 0.1-5.0 microg/ml in presence of Triton X-100 with a minimum detectability limit of 0.06 microg/ml (1.62 x 10(-7) M). The proposed method was successfully applied to commercial tablets containing NDP, the percentage recovery agreed well with those obtained using the official methods. The method was further extended to the in vitro determination of NDP in spiked human urine samples. The % recovery was 102.1 +/- 2.54 (n = 4). A proposal of the reduction reaction pathway was postulated.

Voltammetric determination of josamycin (a macrolide antibiotic) in dosage forms and spiked human urine.

The voltammetric behaviour of josamycin (a macrolide antibiotic) has been studied using direct current (DC(t)) alternating current (AC(t)) and differential pulse polarography (DPP). In Britton-Robinson buffers, josamycin developed cathodic waves over the pH range 7-12. At pH 10, a well-defined cathodic wave with diffusion current constant of 1.06 +/- 0.19 (n = 5) was obtained. The wave was characterized as being diffusion-controlled; and partially affected by adsorption phenomenon. The current-concentrations plots are rectilinear over the range 10-60 and 6-50 microg/ml using DC(t) mode and DPP mode, respectively. The minimum detectability limit was 1.2 microg/ml (1.9 x 10(-6) M) adopting the DPP mode. A method was proposed for the determination of josamycin in its tablets adopting both DC(t) and DPP modes. The results obtained were in good agreement with those given by the manufacturer. The method was extended to the in-vitro determination of the drug in spiked human urine; the % recovery was 98.06 +/- 1.76% (n = 5). The number of electrons involved in the reduction process was accomplished and a proposal of the electrode reaction was presented.

Spectrofluorimetric determination of vigabatrin and gabapentin in urine and dosage forms through derivatization with fluorescamine.

A stability-indicating, sensitive, simple and selective spectrofluorimetric method was developed for the determination of vigabatrin (VG) and gabapentin (GB). The method is based on the reaction between the two drugs and fluorescamine in borate buffer of pH 8.2 to give highly fluorescent derivatives that are measured at 472 nm using an excitation wavelength of 390 nm for both drugs. The optimum conditions were ascertained and the method was applied for the determination of VG and GB over the concentration range of 0.20-4.00 and 0.1-1.0 microg/ml, respectively with detection limits of 0.05 microg/ml (2.9 x 10(-7) M) and 0.06 microg/ml (2.3 x 10(-7) M) for VG and GB, respectively. The suggested method was applied, without any interference from the excipients, to the determination of the two drugs in their pharmaceutical formulations. Furthermore, the method was extended to the in-vitro determination of both drugs in spiked human urine. Interference from endogenous amino acids could be eliminated through selective complexation with copper acetate, the % recovery (n=4) is 98.0 +/- 7.05. Co-administered drugs such as lamotrigine, phenobarbitone, valproic acid, clopazam, carbamazepine, clonazepam and cimitidine did not interfere with the assay. The method is also stability-indicating; as the degradation product of vigabatrin: 5-vinylpyrrolidin-2-one, produced no interference with its analysis.

Voltammetric determination of parthenolide in spiked human plasma and urine.

The voltammetric behaviour of parthenolide, a biologically active sesquiterpene lactone, was studied using direct current (DCt), alternating current and differential-pulse polarography (DPP). Parthenolide developed well-defined cathodic waves over the whole pH range in Britton-Robinson buffers. At pH 10 the diffusion current constant was 3.54 +/- 0.08 (+/- standard deviation; n = 8). The current vs concentration plots were rectilinear over the range 4-36 and 1-28 micrograms/mL in the DCt and DPP modes, respectively, with a minimum detectability of 0.06 microgram/mL (about 1 x 10(-7) M) using the latter technique. The waves were characterised as being diffusion controlled, although adsorption phenomenon played a limited role in the electrode process. The described analytical method was applied to the determination of parthenolide in spiked human urine and plasma; the percentage recoveries were 95.72 +/- 0.22 and 94.0 +/- 0.13 (+/- standard deviation; n = 9), respectively.

Use of 7-fluoro-4-nitrobenzo-2-oxo-1,3-diazole (NBD-F) for the determination of ramipril in tablets and spiked human plasma.

Ramipril, as a secondary amine compound, reacts with 7-fluoro-4-nitrobenzo-2-oxo-1,3-diazole (NBD-F) producing the corresponding fluorescent NBD-ramipril. According to this fact, spectrophotometric and fluorimetric methods for the determination of ramipril were developed. The effect of these parameters on the reaction product were carefully studied to optimize reaction conditions. The relationship between the absorbance at 465 nm and the concentration was found to be linear over the range 1-10 microg/ml. Moreover, the fluorescence intensity was also found to be directly proportional at the concentration over the range of 20-100 ng/ml at 530 nm after excitation at 465 nm. The proposed procedure was successfully applied to the determination of ramipril in both tablet dosage form and in plasma. Spectrophotometric determination of ramipril tablets yielded a percentage recovery of 98.66+/-0.38, while the percentage recovery of spectrofluorimetric determination of ramipril in spiked human plasma was 99.08+/-1.11%. The results obtained are in good agreement with those obtained by the reference method. No interference could be observed from the co-administered drug (hydrochlorothiazines).

Thymoquinone-induced relaxation of guinea-pig isolated trachea.

The effect of thymoquinone (TQ), the main constituent of the volatile oil of black seed (Nigella sativa), on the guinea-pig isolated tracheal zig-zag preparation was investigated. TQ caused a concentration-dependent decrease in the tension of the tracheal smooth muscle precontracted by carbachol. The effects of TQ were significantly potentiated by pretreatment of the tracheal preparations with quinacrine, a phospholipase A2 inhibitor, nordihydroguiaretic acid, a lipoxygenase inhibitor and by pretreatment with methylene blue, an inhibitor of soluble guanylyl cyclase. On the other hand, the effects of TQ were not influenced by pretreatment of the tracheal preparations with indomethacin, a cyclooxygenase inhibitor, propranolol, a non-selective beta-adrenoceptor blocker or by the pretreatment with theophylline, an adenosine receptors antagonist TQ totally abolished the pressor effects of histamine and serotonin on the guinea-pig isolated tracheal and ileum smooth muscles. The results of the present study suggest that TQ induced relaxation of precontracted tracheal preparation is probably mediated, at least in part, by inhibition of lipoxygenase products of arachidonic acid metabolism and possibly by non-selective blocking of the histamine and serotonin receptors. This relaxant effect of TQ, further support the traditional use of black seeds either alone or in combination with honey to treat bronchial asthma.

Electrical stimulation accelerates and increases expression of BDNF and trkB mRNA in regenerating rat femoral motoneurons.

Electrical stimulation promotes the speed and accuracy of motor axonal regeneration. The positive effects of stimulation are mediated at the cell body. Here we characterize the effect of electrical stimulation on motoneuronal expression of BDNF and its receptor, trkB, two genes whose expression levels in motoneurons correlate with regeneration and are regulated by electrical activity in a variety of neurons. We used semiquantitative in situ hybridization to measure expression of mRNA encoding BDNF and the full-length trkB receptor at intervals of 8 h, 2 days and 7 days after unilateral femoral nerve cut, suture, and stimulation. Expression in regenerating motoneurons was compared to that of contralateral intact motoneurons. BDNF and trkB signals were not significantly upregulated 8 h and 2 days after femoral nerve suture and sham stimulation. By 7 days, there was a 2-fold increase in both BDNF and trkB mRNA expression. In contrast, stimulation of cut and repaired nerves for only 1 h led to rapid upregulation of BDNF and trkB mRNA by 3-fold and 2-fold, respectively, within the first 8 h. The stimulation effect peaked at 2 days with 6-fold and 4-fold increases in the signals, respectively. Thereafter, the levels of BDNF and trkB mRNA expression declined to equal the 2-fold increase seen at 7 days after nerve repair and sham-stimulation. We conclude that brief electrical stimulation stimulates BDNF and trkB expression in regenerating motoneurons. Because electrical stimulation is known to accelerate axonal regeneration, we suggest that changes in the expression of BDNF and trkB correlate with acceleration of axonal regeneration.

Voltammetric determination of isoxsuprine and fenoterol in dosage forms and biological fluids through nitrosation.

A simple and highly sensitive voltammetric method was developed for the determination of isoxsuprine HCl (I) and fenoterol HBr (II) in dosage forms and biological fluids. The method is based on treatment of the two compounds with nitrous acid followed by measuring the cathodic current produced by the resulting nitroso derivatives. The voltammetric behavior was studied adopting Direct Current (DCt), Differential Pulse (DPP) and Alternating Current (ACt) polarography. Both compounds produced well-defined, diffusion-controlled cathodic waves over the whole pH range in Britton-Robinson buffers (BRb). At pH 11 and pH 9, the values of diffusion-current constants (Id), were 9.4 +/- 0.3 and 7.7 +/- 0.4 for I and II, respectively. The current-concentration plots for I were rectilinear over the range of 0.6-12 microg/ml and 0.1-12 microg/ml in the DCt and DPP modes, respectively. As for II, the range was 1-20 microg/ml and 0.1-20 microg/ml in the DCt and DPP modes, respectively. The minimum detectability (S/N = 2) were 0.02 microg/ml (approximately 6 x 10(-8) M) and 0.01 microg/ml (approximately 2.6 x 10(-8) M) for I and II, respectively, adopting the DPP mode. The proposed method was applied to the determination of both compounds in dosage forms and the results obtained were in good agreement with those obtained using reference methods. The proposed method was further applied to the determination of isoxsuprine in spiked human urine and plasma. The percentage recoveries adopting the DPP mode were 98.84 +/- 1.18 and 99.26 +/- 0.97, respectively.

Use of mixed anhydrides for the determination of terfenadine in dosage forms and spiked human plasma.

Terfenadine reacts with mixed anhydrides (malonic and acetic anhydrides) producing a yellow-coloured product with intense fluorescence. Based on this fact, a spectrophotometric method was developed for the determination of terfenadine in dosage forms. The relation between the absorbance at 395 nm and the concentration is rectilinear over the range 0.5-5 microg ml(-1) (molar absorptivity is 1.405 x 10(5) l mol(-1) cm (-1)). The reaction product was also measured spectrofluorimetrically at 435 nm after excitation at 395 nm. The fluorescence intensity was directly proportional to the concentration over the range 0.5-4 ng ml(-1) with minimum detectability (S/N = 2) of 0.07 microg ml(-1) (approximately 1.5 x 10(-10) M). The different parameters affecting the development and stability of the reaction product were carefully studied and incorporated into the procedure. The proposed spectrophotometric method was successfully applied to the determination of terfenadine in tablets and suspensions; the percentage recoveries were 99.83 +/- 0.75 and 99.65 +/- 0.83, respectively. The proposed spectrofluorimetric method was applied to the determination of terfenadine in spiked human plasma. The percentage recovery was 99.35 +/- 2.19. The method is highly sensitive and specific. No interference was noticed from co-formulated drugs, such as pseudoephedrine and ibuprofen.

The voltammetric study and determination of ramipril in dosage forms and biological fluids.

The voltammetric behavior of ramipril was studied using cyclic voltammetry, direct current polarography (DCt), differential pulse polarography (DPP) and alternating current polarography (ACt). Ramipril developed well-defined cathodic waves in Britton-Robinson buffers over the pH range 6-12. The waves were characterized as being diffusion-controlled, irreversible and partially affected by adsorption phenomenon. The diffusion-current constant (Id) was 1.24 +/- 0.02. The current-concentration plots were rectilinear over the range 10-50, 4-40 and 0.16-12 micrograms/ml in the DCt, DPP and ACt modes, respectively, with a minimum detectability (S/N = 2) of 0.02 microgram/ml (4.8 x 10(-8) M) using the latter mode. The proposed method was successfully applied to the determination of ramipril in commercial tablets. Hydrochlorothiazide, which is frequently co-formulated with ramipril, did not interfere with the assay. Furthermore, the proposed method was applied to the determination of ramipril in urine and plasma adopting the ACt technique. The percentage recoveries were 97.12 +/- 0.56 and 94.97 +/- 0.62%, respectively. A pathway for the electrode reaction was proposed.

Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration.

Functional recovery is often poor despite the capacity for axonal regeneration in the peripheral nervous system and advances in microsurgical technique. Regeneration of axons in mixed nerve into inappropriate pathways is a major contributing factor to this failure. In this study, we use the rat femoral nerve model of transection and surgical repair to evaluate (1) the effect of nerve transection on the speed of regeneration and the generation of motor-sensory specificity, (2) the efficacy of electrical stimulation in accelerating axonal regeneration and promoting the reinnervation of appropriate muscle pathways by femoral motor nerves, and (3) the mechanism of action of electrical stimulation. Using the retrograde neurotracers fluorogold and fluororuby to backlabel motoneurons that regenerate axons into muscle and cutaneous pathways, we found the following. (1) There is a very protracted period (10 weeks) of axonal outgrowth that adds substantially to the delay in axonal regeneration (staggered regeneration). This process of staggered regeneration is associated with preferential motor reinnervation (PMR). (2) One hour to 2 weeks of 20 Hz continuous electrical stimulation of the parent axons proximal to the repair site dramatically reduces this period (to 3 weeks) and accelerates PMR. (3) The positive effect of short-term electrical stimulation is mediated via the cell body, implicating an enhanced growth program. The effectiveness of such a short-period low-frequency electrical stimulation suggests a new therapeutic approach to accelerate nerve regeneration after injury and, in turn, improve functional recovery.