• Journal of Pharmaceutical Investigation
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• 제16권2호
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• pp.43-54
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• 1986

To increase the bioavailability of clonixin, clonixin argininate was prepared and compared with clonixin by determining solubility, pKa, lipid-water partition coefficient, dissolution rate and in vivo tests. The results are summerized as followings; 1) The solubility of clonixin argininate was increased by 20 times in water, about 1.2 times in pH 1.2 and pH 8.0 buffer solution, and about 1.8 times in pH 6.8 buffer solution compared with that of clonixin. 2) pKa values of clonixin, clonixin lysinate and clonixin argininate were 6.32, 7.20 and 7.45, respectively. 3) The lipid-water partition coefficient of clonixin argininate was increased more than that of the clonixin in n-hexane, carbon tetrachloride, chloroform, methylene chloride, and n-butanol, but the partition coefficient of clonixin was increased more than that of clonixin argininate in benzene/pH 1.2 buffer solution, ether/pH 8.0 buffer solution, and 3-methylbutyl acetate/pH 1.2, pH 8.0 buffer solution. 4) The time required to dissolve 60% $(T_{60%},\;min.)$ of clonixin argininate was about 1.5 min. in water and pH 1.2 buffer solution, and about 5 min. in pH 6.8 buffer solution. $T_{60%}$ of clonixin lysinate was about 1.5 min. in water, about 1.8 min. in pH 6.8 buffer solution, and about 8 min. in pH 1.2 buffer solution. But $T_{60%}$ of clonixin was about 96 min. in pH 6.8 buffer solution, over 2 hours in water and pH 1.2 buffer solution. 5) Anti-inflammatory effect of clonixin argininate was increased more than that of clonixin over 6 hours, and that of clonixin lysinate was followed by lapse of time. 6) Analgesic effect of clonixin argininate was increased by 1.5 times more than that of clonixin and the effect of clonixin argininate was nearly identical with that of clonixin lysinate. 7) The absorption rates (Ka) of clonixin, clonixin lysinate and clonixin argininate were $0.169\;hr^{-1},\;0.652\;hr^{-1}$ and $0.723\;hr^{-1}$ in situ, respectively.

• 한국치위생학회지
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• 제17권5호
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• pp.911-919
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• 2017

Objectives: The baobab tree is a multipurpose, widely-used species with medicinal properties and numerous food uses. The aim of study was to evaluate the effect of oral administration of baobab on the formalin-induced inflammatory pain in rat model injected into the orofacial regions. Methods: Male Sprague-Dawley rats weighing 260-280 g were used. Pain in the orofacial region was induced using two models, 5% formalin was injected $50{\mu}l$ subcutaneously or $30{\mu}l$ in temporomandibular joint (TMJ), respectively. Rats were divided into 4 groups (n=6); formalin, formalin after distilled water (vehicle) or baobab (150, 300 mg/kg). The number of noxious behavioral responses with scratching the facial region was recorded for 9 successive 5-min intervals following formalin injection. Results:There was no significant difference in the first response to the pain between the formalin induced group and the drug administration group. However, in the secondary infusion group, all of the pain medication were responded (Bao 150, 300 mg/kg) (p<0.05). Conclusions:The results showed analgesic effect of baobab on formalin-induced orofacial inflammatory pain. This suggests that the natural product is an effective alternative to the postinflammatory pain control.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.307-312
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• 1998

This study was performed to investigate the mechanism of central analgesic effects of antidepressants. Thirty four male rats were anesthetized with pentobarbital sodium (40 mg/kg, ip). A stainless steel guide cannula and a PE tube (PE10) were implanted into the lateral ventricle and cisterna magna area. Stimulating and recording electrodes were implanted into the incisor pulp and anterior digastric muscle. Electrodes were led subcutaneously to the miniature cranial connector sealed on the top of the skull with acrylic resin. The jaw opening reflex was used in freely moving rats, and antidepressants were administered intracisternally in order to eliminate the effects of anesthetic agents on the pain assessment and evaluate the importance of the central action site of antidepressants. After 48 hours of recovery from surgery, digastric electromyogram (dEMG) of freely moving rats was recorded. Electrical shocks (200 ${\mu}sec$ duration, 0.5-2 mA intensity) were delivered at 0.5 Hz to the dental pulp every 2 minute. Intracisternal administration of $15\;{\mu}g$ imipramine suppressed dEMG elicited by noxious electrical stimulation in the tooth pulp to $76{\pm}6%$ control. Intracisternal administration of $30\;{\mu}g$ desipramine, nortriptyline, or imipramine suppressed dEMG remarkably to $48{\pm}2,\;27{\pm}8,\;or\;25{\pm}5%$ of the control, respectively. Naloxone, methysergide, and phentolamine blocked the suppression of dEMG produced by intracisternal antidepressants from $23{\pm}2\;to\;69{\pm}4%,\;from\;32{\pm}5\;to\;80{\pm}9%,\;and\;from\;24{\pm}6\;to\;77{\pm}5%$ of the control, respectively. These results indicate that antidepressants produce antinociception through central mechanisms in the orofacial area. Antinociception of intracisternal antidepressants seems to be mediated by an augmentation of descending pain inhibitory influences on nociceptive pathways.

• The Korean Journal of Physiology and Pharmacology
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• 제20권5호
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• pp.525-531
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• 2016

The analgesic mechanism of opioids is known to decrease the excitability of substantia gelatinosa (SG) neurons receiving the synaptic inputs from primary nociceptive afferent fiber by increasing inwardly rectifying $K^+$ current. In this study, we examined whether a ${\mu}$-opioid agonist, [D-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO), affects the two-pore domain $K^+$ channel (K2P) current in rat SG neurons using a slice whole-cell patch clamp technique. Also we confirmed which subtypes of K2P channels were associated with DAMGO-induced currents, measuring the expression of K2P channel in whole spinal cord and SG region. DAMGO caused a robust hyperpolarization and outward current in the SG neurons, which developed almost instantaneously and did not show any time-dependent inactivation. Half of the SG neurons exhibited a linear I~V relationship of the DAMGO-induced current, whereas rest of the neurons displayed inward rectification. In SG neurons with a linear I~V relationship of DAMGO-induced current, the reversal potential was close to the $K^+$ equilibrium potentials. The mRNA expression of TWIK (tandem of pore domains in a weak inwardly rectifying $K^+$ channel) related acid-sensitive $K^+$ channel (TASK) 1 and 3 was found in the SG region and a low pH (6.4) significantly blocked the DAMGO-induced $K^+$ current. Taken together, the DAMGO-induced hyperpolarization at resting membrane potential and subsequent decrease in excitability of SG neurons can be carried by the two-pore domain $K^+$ channel (TASK1 and 3) in addition to inwardly rectifying $K^+$ channel.

• 생약학회지
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• 제45권3호
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• Archives of Plastic Surgery
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• 제47권1호
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• pp.15-19
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• 2020

Background Pain caused by nasal pack removal after closed reduction of nasal bone fractures is a common problem. This study investigated the effect of infiltrating lidocaine into nasal packs on the pain caused by pack removal after closed reduction of nasal bone fractures. Methods Seventy-five patients who underwent closed reduction of nasal bone fractures between March 2016 and March 2018 were enrolled in this prospective, randomized, single-blind study. Merocel (hydroxylated polyvinyl acetate) packs were applied bilaterally and retained for 5 days. Twenty minutes before removal, both packs were rehydrated with 6 mL of 2% lidocaine in 26 patients and with 6 mL of saline in 24 patients; the packs were not rehydrated in 25 patients. Visual analog scale (VAS) scores for pain on removal were recorded. Results The mean VAS score was 5.3±2.0 in all patients, 3.8±1.5 in the lidocaine group, 5.8±1.4 in the saline group, and 6.3±2.1 in the non-rehydrated group. There was a significant difference in the pain score between the lidocaine and saline groups (P<0.001) but not between the saline and non-rehydrated groups (P=0.186). Conclusions Infiltration of lidocaine into Merocel packs reduced the pain caused by pack removal after closed reduction of nasal bone fractures.

• 대한수의학회지
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• 제42권1호
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• pp.123-130
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• 2002

To investigate the cardiopulmonary and anesthetic effects of propofol in dogs, experimental dogs were randomly divided into 4 groups (propofol infusion anesthesia, P/INF, propofol intermittent anesthesia, P/INTER, propofol induction anesthesia, P/ISO, thiopental Na induction anesthesia, T/ISO) and monitored analgesic and anesthetic effects, recovery time, body temperature, heart rate, mean arterial pressure, respiratory rate, systolic and diastolic pressure. In all groups, apnea was not observed. In the P/INF group, the respiratory rate(RR) was slightly decreased, but in the P/INTER group, RR was increased and shallowing. In the groups of P/ISO and T/ISO, the respiratory rate was decreased. Heart rate(HR) was increased after induction anesthesia in all groups, but gradually decreased. Mean arterial pressure(MAP) was decreased after injection anesthesia in the groups of P/INF and P/INTER. In the groups of P/ISO and T/ISO, however, MAP was slightly increased. Systolic and diastolic arterial pressure were gradually decreased after induction anesthesia, but not significantly. In the groups of P/INF and P/ISO, recovery time was shorter than the groups of P/INTER and T/ISO. In all groups, body temperature of animals was decreased gradually according to time but no significant changes were observed. Propofol injection doesn't make the complete loss of responses of animals, especially, in the P/INTER group. In the P/INF group, deep pain was present until the end of anesthetic period. During recovery period, any other side effects except incoordination were not monitored. The present study suggested that infusion anesthesia was superior to intermittent anesthesia as injection anesthetic agent, and propofol was better than thiopental Na as induction anesthetic agent.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.558-562
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• 2014

Tramadol is an opioid analgesic agent that has been the subject of a series of case reports suggesting potential for misuse or abuse. However, it is not a controlled substance and is not generally considered addictive in Korea. In this study, we examined the dependence potential and abuse liability of tramadol as well as its effect on the dopaminergic and serotonergic systems in rodents. In animal behavioral tests, tramadol did not show any positive effects on the experimental animals in climbing, jumping, and head twitch tests. However, in the conditioned place preference and self-administration tests, the experimental animals showed significant positive responses. Taken together, tramadol affected the neurological systems related to abuse liability and has the potential to lead psychological dependence.

• Korean Journal of Acupuncture
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• 제22권1호
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• pp.133-150
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• 2005

Objective : The purpose of this study is to examine the tendency of experimental studies on the physiological effects of acupuncture at $ST_{36}$(Zusanli). Methods : We investigated 69 theses (10 Korean and 59 international) which were searched by the keyword 'Zusanli' through PubMed website, and that were experimented with manual acupuncture or electroacupuncture on healthy human subjects or normal animals. Results : The 69 theses were classified into iou groups based on the main topic which is related with the influence of acupuncture stimulation at $ST_{36}$(Zusanli), such as digestive system, nervous system, immune system, and cardiovascular system. The main results found in this study are : 1. Acupuncture at $ST_{36}$(Zusanli) increases gastric mobility. And such effect is related with vagal nerve and opioid pathway. 2. Acupuncture at $ST_{36}$(Zusanli) is valuably related with cerebral cortex. And it influences on the cerebrum activities. 3. Acupuncture at $ST_{36}$(Zusanli) has noticeable analgesic effect, which is related with Opioid mechanism, Gate control and SP 4. Acupuncture at $ST_{36}$(Zusanli) increases immunity Conclusion . Acupuncture at $ST_{36}$(Zusanli) has many effects on digestive system, nervous system, immune system, and cardiovascular system.

• Korean Journal of Acupuncture
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• 제26권2호
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• pp.61-74
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• 2009

Objectives: The warm needling technique is a method which combines the effects of acupuncture with those of moxibustion. The purpose of this study was to find the stimulus effects of a high frequency warm needling device when stimulating acupoint $LI_4$ on the carrageenan-induced arthritis. Methods: This study was to observe the effects to edema reaction, WBF(weight bearing force), NO concentration, nNOS expression after the electro high frequency stimulus of high frequency warm needling device on LI4 with insulated acupuncture needle. Results: The effect of the high frequency warm needling device is to rise up the temperature in proportion to the current intensity. After stimulating on the acupoint $LI_4$ of the carrageenan-induced arthritis in rats with the high frequency warm needling device, it significantly reduced edema in the rat's foot. In addition, WBF, NO concentration of spinal cord (nmol/mg), and nNOS relative expression were reduced. Conclusions: The above results support the idea that stimulus by the high frequency warm needling device on $LI_4$ produces a potent analgesic effect in the arthritis pain model of the rat. Moreover, stimulus by the high frequency warm needling device modulates endogenous NO through the suppression of nNOS protein expression.