• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.37-47
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• 1988

Xylazine hydrochloride is a widely used analgesic, sedative and muscle relaxant agent in veterinary clinic. Yohimbine hydrochloride and 4-aminopyridine are known as antagonists of xylazine hydrochloride. This paper was investigated to know that the effect of xylazine hydrochloride, yohimbine hydrochloride and 4-aminopyridine, and that whether or not antagonism of yohimbine hydrochloride and 4-aminopyridine to xylazine hydrochloride-induced effect on gizzard motility in chicken. The results were as follows. 1. After xylazine hydrochloride administration, the gizzard motility in chicken was instantly inhibited in relaxation state, and this state was prolonged in proportion to increase of dose. 2. After yohimbine hydrochloride administration, the gizzard motility in chicken showed increase of contractile frequency. 3. After 4-aminopyridine administration, the gizzard motility in chicken was gradually recovered next to decrease of contractile amplitude and frequency. 4. After the combination of yohimbine hydrochloride and 4-aminopyridine administration, the gizzard motility in chicken showed increase of amplitude and radical increase of frequency. 5. After xylazine hydrochloride administration, the relaxation time was shortened by yohimbine hydrochloride, 4-aminopyridine and the combination of yohimbine hydrochloride and 4-aminopyridine. In conclusion, the gizzard motility in chicken was inhibited by xylazine hydrochloride, and this effect was antagonized by the combination of yohimbine hydrochloride and 4-aminopyridine.

• Korean Journal of Veterinary Research
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• v.30 no.1
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• pp.113-121
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• 1990

The present study was undertaken to determine the effect of xylazine-pentobarbital anesthesia on the gastroduodenal transit time of barium sulfate and whether this condition can be antagonized by yohimbine, 4-aminopyridine and yohimbine+4-aminopyridine in dogs. Xylazine-pentobarbital anesthesia prolonged the gastroduodenal transit time to $121.50{\pm}21.25$ minutes compared with $5.25{\pm}0.90$ minutes of control. Yohimbine and yohimbine+4-aminopyridine reversed $121.50{\pm}21.25$ minutes of transit time of anesthetized dog to $25.25{\pm}6.83$ and $63.25{\pm}15.69$ minutes, respectively. 4-aminopyridine alone, $115.75{\pm}$18.35 minutes, was not effective in reversing the xylazine-pentobarbital-induced prolongation of gastroduodenal transit time. Yohimbine was the most effective for reversal of xylazine-pentobarbital-induced prolongation of gastroduodenal transit time in dogs.

• Journal of the Korean Chemical Society
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• v.57 no.3
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• pp.341-351
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• 2013

Zn(II), Cd(II) and Hg(II) complexes with a general composition[$M(L)_2(X)_2$], where L=4-aminopyridine (4AP) and $X=NO_2{^-}$ were prepared under microwave irradiation. The metal complexes were characterized by elemental analyses, molar conductance, IR, Far-IR, electronic, NMR ($^1H$, $^{13}C$), XPS spectral and thermal studies. The spectroscopic studies reveal the composition, different modes of bonding, electronic transition, different chemical environment of C and H atoms and the electronic state of the metal atoms. On the basis of the characterization data, tetrahedral geometry is suggested for all the complexes. The free ligand (4-aminopyridine) and their metal complexes were screened against phytopathogenic fungi and bacteria in vitro and the activities were compared.

• Bulletin of the Korean Chemical Society
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• v.33 no.2
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• pp.535-540
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• 2012

A series of benzamide-based histone deacetylases (HDACs) inhibitors possessing N-(aminopyridine) residue as the zinc binding site of HDAC were synthesized and evaluated. Among these derivatives, compounds with N-(2-amino-4-pyridine) benzamide moiety have been found as the most potent ones. Moreover, introduction of appropriate substituents on the terminal aryl group acting as the surface-recognition domain could significantly improve the antiproliferative activity. In particular, the compound 4k possessed favorable pharmacokinetic characteristics and exhibited potent antitumor activity on xenograft model in mice at well tolerated doses, thus suggesting a good therapeutic index.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.463-469
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• 2000

It has been well known that 4-aminopyridine (4-AP) has an excitatory effect on vascular smooth muscle due to causing membrane depolarization by blocking $K^+-channel$. However, we observed that 4-AP had an inhibitory effect on the mesenteric artery of rat. Therefore, we investigated the mechanism of 4-AP-induced vasorelaxation. The mesenteric arcuate artery and its branches were isolated and cut into ring. The ring segment was immersed in HEPES-buffered solution and its isometric tension was measured. 4-AP $(0.1{\sim}10\;mM)$ induced a concentration-dependent relaxation, which was unaffected by NO synthase inhibitor, $N^G-nitro-L-arginine$ methylester $(100\;{\mu}M)$ or soluble guanylate cyclase inhibitor, methylene blue $(100\;{\mu}M).$ Glibenclamide $(100\;{\mu}M)$, ATP-sensitive $K^+$ channel blocker, did not exert any effect on the 4-AP-induced vasorelaxation. 4-AP relaxed the sustained contraction induced by 100 mM $K^+$ or $Ca^{2+}$ ionophore, A23187 $(100\;{\mu}M)$ in a dose-dependent manner. In addition, 4-AP significantly decreased the phasic contractile response to norepinephrine in the absence of extracellular $Ca^{2+}$. However, 4-AP did not block the $^{45}Ca$ influx of rat aorta. From the above results, we suggest that 4-AP may not block the $Ca^{2+}$ influx through $Ca^{2+}-channel,$ but act as a nonspecific vasorelaxant in arterial smooth muscle.

• Journal of the Korean Chemical Society
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• v.57 no.6
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• pp.712-720
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• 2013

Microwave assisted syntheses of Zn(II), Cd(II) and Hg(II) complexes with 3-aminopyridine (3AP) and nitrite ($NO_2{^-}$) ions have been reported. The metal complexes were characterized by elemental analyses, molar conductance, IR, Far-IR, electronic, NMR ($^1H$, $^{13}C$), thermal and electron impact mass spectral studies. The spectroscopic studies reveal the composition, the nature of nitrite ligand in the complexes, electronic transitions, chemical environments of C and H atoms thermal degradation of the complexes. On the basis of characterization data, distorted tetrahedral geometry is suggested for Zn(II), Cd(II) and Hg(II) complexes. The organic ligand (3AP) and their metal complexes were screened against gram negative pathogenic bacteria and fungi in vitro. The results are compared with our previous report J. Korean Chem. Soc. 2013, 57, 341 on 4-aminopyridine and nitrite ion complexes of the same metal ions.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.453-460
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• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.385-391
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• 2000

Using the patch-clamp technique, we investigated the alteration of 4-aminopyridine(4-AP)-sensitive, voltage-dependent $K^+$ channel (Kv) in the mesenteric arterial smooth muscle cell (MASMC) of renovascular hypertensive model, one-kidney one-clip Goldblatt hypertensive rat (GBH). To isolate $K_V$ current, internal pipette solution contained 5 mM ATP and 10 mM EGTA. Under these condition, MASMC was depolarized by 4-AP, but charybdotoxin did not affect membrane potential. Membrane potential of hypertensive cell $(-40.3{\pm}3.2\;mV)$ was reduced when compared to that of normotensive cell $(-59.5{\pm}2.8\;mV).$ Outward $K^+$ current of hypertensive cell was significantly reduced when compared to normotensive cell. At 60 mV, the outward currents were $19.10{\pm}1.91$ and $14.06{\pm}1.05$ pA/pF in normotensive cell and hypertensive cell respectively. 4-AP-sensitive $K^+$ current was also smaller in hypertensive cell $(4.28{\pm}0.38\;pA/pF)$ than in normotensive cell $(7.65{\pm}0.52\;pA/pF).$ The values of half activation voltage $(V_{1/2})$ and slope factor (k1) as well as the values of half inactivation voltage $(V_{1/2})$ and slope factor (k1) were virtually similar between GBH and NTR. These results suggest that the decrease of 4-AP-sensitive $K^+$ current contributes to a depolarization of membrane potential, which leads to development of vascular tone in GBH.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.1
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• pp.25-28
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• 2003

Ion channel inhibitors are widely used for pharmacological discrimination between the different channel types as well as for determination of their functional role. In the present study, we tested the hypothesis that 4-aminopyridine (4-AP) could affect the large conductance $Ca^{2+}$-activated $K^+$ channel ($BK_{Ca}$) currents using perforated-patch or cell-attached configuration of patch-clamp technique in the rabbit pulmonary arterial smooth muscle. Application of 4-AP reversibly inhibited the spontaneous transient outward currents (STOCs). The reversal potential and the sensitivity to charybdotoxin indicated that the STOCs were due to the activation of $BK_{Ca}$. The $BK_{Ca}$ currents were recorded in single channel resolution under the cell-attached mode of patch-clamp technique for minimal perturbation of intracellular environment. Application of 4-AP also inhibited the single $BK_{Ca}$ currents reversibly and dose-dependently. The membrane potential of rabbit pulmonary arterial smooth muscle cells showed spontaneous transient hyperpolarizations (STHPs), presumably due to the STOC activities, which was also inhibited by 4-AP. These results suggest that 4-AP can inhibit $BK_{Ca}$ currentsin the intact rabbit vascular smooth muscle. The use of 4-AP as a selective voltage-dependent $K^+$ (KV) channel blocker in vascular smooth muscle, therefore, must be reevaluated.

• Journal of the Korean Electrochemical Society
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• v.17 no.1
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• pp.30-36
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• 2014

Redox complexes to transport electrons from enzyme to electrodes are very important part in glucose sensor. Pentacyanoferrate-bound aniline ($Fe(CN)_5$-aminopyridine), was prepared as a potential redox mediator in a glucose dehydrogenase (GDH)-glucose sensor. The synthesized pyridyl-$NH_2$ to pentacyanoferrate was characterized by the electrochemical and spectroscopic methods. A amperometric enzyme-linked electrode was developed based on GDH, which catalyses the oxidation of glucose. Glucose was detected using GDH that was co-immobilized with an $Fe(CN)_5$-aminopyridine and gold nano-particles (AuNPs) on ITO electrodes. The $Fe(CN)_5$-aminopyridine and AuNPs immobilized onto ITO electrodes provided about a two times higher electrochemical response compared to that of a bare ITO electrode. As glucose was catalyzed by wired GDH, the electrical signal was monitored at 0.4 V versus Ag/AgCl by cyclic voltammetry. The anode currents was linearly increased in proportion to the glucose concentration over the 0~10 mM range.