• Archives of Pharmacal Research
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• 제29권5호
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• pp.400-404
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• 2006

This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin $(10^{-6}\;M)$ suppressed the electrically stimulated (0.5-5 Hz) relaxation of the LES. However, guanethidine $(10^{-6}\;M)$ and atropine $(10^{-6}\;M)$ had no effect indicating that the relaxations were neurally mediated via the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester ($10^{-4}M$, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60% inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA ($10^{-3}-10^{-5}M$, non selective receptor agonist), muscimol ($10^{-3}-10^{-5}M$, GABA-A agonist), and baclofen ($10^{-3}-10^{-5}M$, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline ($10^{-5}M$, GABA-A antagonist) and phaclofen ($10^{-5}M$, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.

• International Journal of Oral Biology
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• 제30권3호
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• pp.91-98
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• 2005

Gamma-aminobutyric acid (GABA) is known as an inhibitory neurotransmitter in the neurons of the central nervous system. However, its detailed action mechanisms in the rostral gustatory zone of the nucleus tractus solitarius (rNTS) have not been established. The present study was aimed to investigate the distribution, role and action mechanisms of GABA in rNTS. Membrane potentials were recorded by whole cell recordings in isolated brain slices of the rat medulla. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in the neurons in rNTS. The change in input resistance ws accompanied by response to a depolarizing pulse were diminished by GABA. Superfusion of the slices with either $GABA_A$ agonist, muscimol, $GABA_B$ agonist, baclofen or $GABA_C$ agonist, TACA, decreased input resistance and reduced the nerve activity in association with membrane hyperpolarization. It is suggested that inhibitory signals playa role in sensory processing by the rNTS, in that GABA actions occur through activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptor. These results suggest that GABA has an inhibitory effect on the rNTS through an activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptors and that the GABAergic inhibition probably plays an important role in sensory processing by the rNTS.

• 약학회지
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• 제58권5호
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• pp.328-336
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• 2014

Anticholinergic drugs are included in the efficacy group of various antidepressants, antihistamines, antispasmodics like skeletal muscle relaxants. Elderly patients are often taking anticholinergic drugs due to various diseases such as sleep disorders and dysuria. But the use of anticholinergic drugs is restricted in guidelines such as Beers Criteria or STOPP due to the anticholinergic adverse effects including dry mouth, constipation, difficult urination, delirium, hallucinations and especially cognitive impairment. In this study, we investigated the usage of anticholinergic drugs in out-of-hospital prescription of 4,442 elderly patients. Results of the study were obtained that 32% (n=1,421) of overall patients were prescribed with 1~6 products (average 1.37) of anticholinergic drugs. 70.9% of the 1,421 patients (n=1,007) were prescribed with one drug, 22.7% (n=323) were two drugs and 4.9% (n=70) were three drugs. 27.1% of the 1,421 patients (n=430) were 70~74 years old patients who were the most commonly prescribed with anticholinergic drugs. Amitriptyline, chlorpheniramine, dimenhydrinate and quetiapine were most frequent component of ACB Score 3 drugs and amantadine, baclofen, carbamazepine, cyproheptadine and oxcarbazepine were most frequent of ACB Score 2 drugs. Anticholinergic Drug Scale (ADS) of individual patients presented one point (48.5%, n=689), 2 points (15.4%, n=219), more than 3 points (36.1%, n=513), and up to maximum 12 point (n=1). More than 2 points were more than half (51.5%, n=732). Therefore, additional prospective study in the use and adverse effects of anticholinergic drugs for elderly patients will be required. And national management such as DUR program will be required for elderly drug administration from now on.

• 한방안이비인후피부과학회지
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• 제13권2호
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• pp.112-139
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• 2000

I examined and referred to literatures of every generations on the nicknames, causes, herb medications and acupucture treatments of ptosis(上胞下垂). And then the results were obtained as follows. We've compared and analyzed Occidental and Oriental medical causes, symptoms and treatments of Primary trigeminal neuralgia and wanted to get better effects by a cooperative analysis. So the examination and analysis of the recent treatment tendency and reference bibliography show the following results. 1. Trigeminal neuralgia is nerve systematic disease appearing in the distribution scope of trigeminal nerve. It's characterized by extreme pain accompanying with a repeated and simultaneous fit from several seconds to 1-2 minutes. 2. Though there are many hypothesis on the trigeminal neuralgia, but now many doctors agree that when trigeminal nerve is under the local out of sheath conditions resulting from receiving a chronic stimulus, and the nucleus of trigeminal nerve fire, owing to decrease of pain control function and abnormal occurrence of action potential, it would be appeared. 3. The Oriental medical name of trigeminal neuralgia is generally Dootong, Doopoong, Myuntong, Pyundootong, Pyundoopoong, and Myuntong is the nearest in Occidental medicine. 4. The Oriental medical cause of trigeminal neuralgia is usually divided into Wekam and Naesang. The first one is caused by Poonghan, Poongyul, Damhwa and wicked energy enter into the body, the mechanical energy is obstructed and can't move any more, so the pain appears by them. The other cause is the hurt by emotion. And it would be loss of the transportain of liver and obstructed, so result into Kanwulhwahwa, Kanpoongnaedong and the pain appears. 5. There are two methods of curing trigeminal neuralgia. As a medication, primary method is prescribing Carbamazepine and the second is using Phenytoin or Baclofen. And as a operation, Drug injection of trigeminal nerve, Amputation of branches of trigeminal nerve, Retrogasserian glycerol rhizotomy, Radiofrequency gangliolysis, Neurovascular decompression can be used. 6. There are several herb medicines for Trigeminal neuralgia. First, Chungung is good for Hwaejeetong, Keopoongjedam, Hwalhyuljeetong. Second, Jeongal, Jiryong, Okong is used for Sikpoonghekyung, Tongkyungjeetong. Third, Baekjee, Sesin, Cheonma, Manhyungja is efficacious in Sinonhepyo. Sanpoongjeetong. Fourth, for falling of liver's Wulhwa, Yongdamcho, Hyungge, Kukwha can be used. And also Saengjihwang, Hwangkm is good for going down the fever of Yangmyungwiyul and finally, Baekkangjam. Moryu can be effective for Jaumjamyang, Haekyungjitong. The other medicines can be used as assistant analgesics, and it also efficacious. 7. Generally the points of pain on the face and the points of Soyangkyung and Yangmyungkyung is used for Acupuntual therapy, because the two meridians passed on the face. Hakwan. Sabaek, Kwanryo, Keoryo, Hyubkeo, Taeyang, Jeechang, Younghyang, Eoyo, Chanjuk. Yangbaek. Sajukkong. Dooyoo, Kwangsangjum, Sengjang, Poongjee is used for taking near point and Joksamlee, Naejung, Habkok is used for taking distant point. 8. Dansam or Danggui injection which have a effect for Hwalhyulhwaeo, Sokyunghwalak and Vit B1, Vit B2, Vit B12, $2\%$ Hydrochloroprocaine, $1\%$ Lidocaine injection to pain point for local analgesics had so good effect. And external application and moxibustion are used for another treatment. 9. It proved that through mouse model, both Herb medication group and Drug medication group are efficacious for trigeminal neuralgia similarly and also the cooperative medication group shows more effective result than the only drug medication group.

• The Korean Journal of Physiology and Pharmacology
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• 제14권2호
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• pp.59-69
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• 2010

Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following peripheral nerve injury has been postulated to mediate neuropathic pain. In the present study, we tested whether neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after peripheral nerve injury was related to the impairment of GABAergic inhibition or neuropathic pain. To these aims, we first analyzed the pain behaviors following the spinal administration of GABA antagonists ($1{\mu}g$ bicuculline/rat and $5{\mu}g$ phaclofen/rat), agonists ($1{\mu}g$ muscimol/rat and $0.5{\mu}g$ baclofen/rat) or GABA transporter (GAT) inhibitors ($20{\mu}g$ NNC-711/rat and $1{\mu}g$ SNAP-5114/rat) into naive or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal GABA, its synthesizing enzymes (GAD65, 67) and its receptors (GABAA and GABAB) and transporters (GAT-1, and -3) between two groups of rats with different severity of neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of GABA antagonists markedly lowered tail-withdrawal threshold in naive animals, and GABA agonists or GAT inhibitors significantly attenuated neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of neuropathic pain following peripheral nerve injury.

• International Journal of Oral Biology
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• 제40권3호
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• pp.117-125
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• 2015

The present study investigated the role of central $GABA_A$ and $GABA_B$ receptors in orofacial pain in rats. Experiments were conducted on Sprague-Dawley rats weighing between 230 and 280 g. Intracisternal catheterization was performed for intracisternal injection, under ketamine anesthesia. Complete Freund's Adjuvant (CFA)-induced thermal hyperalgesia and inferior alveolar nerve injury-induced mechanical allodynia were employed as orofacial pain models. Intracisternal administration of bicuculline, a $GABA_A$ receptor antagonist, produced mechanical allodynia in naive rats, but not thermal hyperalgesia. However, CGP35348, a $GABA_B$ receptor antagonist, did not show any pain behavior in naive rats. Intracisternal administration of muscimol, a $GABA_A$ receptor agonist, attenuated the thermal hyperalgesia and mechanical allodynia in rats with CFA treatment and inferior alveolar nerve injury, respectively. On the contrary, intracisternal administration of bicuculline also attenuated the mechanical allodynia in rats with inferior alveolar nerve injury. Intracisternal administration of baclofen, a $GABA_B$ receptor agonist, attenuated the thermal hyperalgesia and mechanical allodynia in rats with CFA treatment and inferior alveolar nerve injury, respectively. In contrast to $GABA_A$ receptor antagonist, intracisternal administration of CGP35348 did not affect either the thermal hyperalgesia or mechanical allodynia. Our current findings suggest that the $GABA_A$ receptor, but not the $GABA_B$ receptor, participates in pain processing under normal conditions. Intracisternal administration of $GABA_A$ receptor antagonist, but not $GABA_B$ receptor antagonist, produces paradoxical antinociception under pain conditions. These results suggest that central GABA has differential roles in the processing of orofacial pain, and the blockade of $GABA_A$ receptor provides new therapeutic targets for the treatment of chronic pain.

• Journal of Yeungnam Medical Science
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• 제9권2호
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• pp.359-381
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• 1992

Benzodiazepine계 약물들은 진정 최면제의 대표적인 약물로서, 중추신경계에서의 그 작용은 gamma amino butyric acid(GABA) 수용체와 짝지워져 있는 benzodiazepine 수용체를 통해서 나타나며 또한 뇌에 있는 synaptosome에서 전위 의존성 calcium channel을 통한 calcium의 섭취를 억제함으로써 진정작용 및 최면 작용이 나타난다. 이와 아울러 말초 장기에서도 benzodiazepine 수용체와 GABA 수용체가 발견 되었는데 이들의 기능과 상호관계는 잘 알려져 있지 않다. 이에 본 실험에서는 benzodiazepine계통의 대표적인 약물이며 중추신경과 말초 장기에 동시에 작용하는 diazepam이 흰쥐 적출자궁의 자발 수축 및 oxytocin 유발 수축에 미치는 영향을 검색하고, 이러한 diazepam의 효과와 GABA 수용체 및 calcium과의 상호관계를 검색함으로써 그 작용기전을 추구해 보기 위하여 다음과 같은 실험을 하였다. 난소를 제거한 후 estrogen(17 beta-estradiol : $500{\mu}g/kg/day$)을 4일 동안 전 처치한 흰쥐의 자궁을 적출하여 등척성 장력을 측정함으로써 그 수축력의 변화를 관찰하였다. Diazepam과 GABA 수용체 효현제 및 그 봉쇄제들이 자궁절편의 자발 수축과 oxytocin 유발 수축에 미치는 영향을 검색하였고, 또 이들 약물의 작용에 관련된 calcium 동원기전에 대하여 관찰하여 다음과 같은 결과를 얻었다. Diazepam은 흰쥐 적출자궁의 자발수축 및 oxytocin 유발수축을 농도 의존적으로 억제하였다. GABA, GABA A 수용체 효현제인 muscimol, GAGA A 수용체의 상경적 봉쇄제인 bicuculline, GABA A 수용체의 비상경적 봉쇄제인 picrotoxin, GABA B 수용체 효현제인 boclofen, 그리고 GABA B 수용체 봉쇄제인 delta-aminovaleric acid는 흰쥐 적출 자궁의 자발 수축 및 oxytocin 유발수축에 아무런 영향을 미치지 않았다. 자발 수축 및 oxytocin 유발수축에 대한 diazepam의 억제 작용은 GABA 수용체 효현제 및 봉쇄제의 영향을 받지 않았다. 그러나 bicuculline은 diazepam의 억제 작용에 상가적으로 작용하였는데, bicuculline의 이러한 작용은 muscimol에 의해서 길항되지 않았다. 정상 PSS 내에서 diazepam에 의해 억제되었던 자발수욱 및 oxytocin유발수촉은 calcium의 첨가 및 calcium inophore인 A23187의 첨가로 일부 회복되었다. Calcium 배제 용액내에서는 diazepam이 calcium 첨가로 인한 수축력 회복을 방해하였으며 calcium inophore인 A23187에 의한 수축력 증가는 막지 못하였다. 또 세포외액에 calcium이 결핍된 상태에서는 oxytocin 자체에 의한 수축을 방해하지 못하였으나 이어 첨가된 calcium에 의한 oxytocin 유발 수축의 증가는 일부 억제하였다. 이상의 실험결과로 미루어 볼 때 diazepam은 자궁의 자발수측 및 oxytocin 유발 수축을 억제할 수 있으며, 이러한 작용은 GABA 수용체 의존성이 아닌 세포외액의 calcium의 유입을 억제함으로써 나타나는 것으로 사료된다.

• Journal of Oral Medicine and Pain
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• 제34권2호
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• pp.207-216
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• 2009

2003년부터 2008년까지 경북대학교병원 구강내과를 내원한 삼차신경통 환자 90명의 임상 소견 및 약물 치료에 대한 결과를 분석하여 다음과 같은 결론을 얻었다. 1. 삼차신경통 환자는 40대 이상이 94.4%를 차지하였고 남녀비가 1:2.1로 여성에서 거의 2배 정도 호발하였다. 2. 삼차신경의 상악분지에 단독으로 이환된 경우가 51.1%로 가장 많았고 좌우비가 1:2.9로 우측에 더 자주 발생하였다. 3. 85명(94.4%)의 환자가 경북대학교병원 구강내과에 내원하기 전 삼차신경통을 치료하기 위해 다른 의료기관을 내원한 경험이 있었다. 3. 40명(44.4%)의 환자가 현재 치료 중인 전신질환을 가지고 있었다. 4. Carbamazepine 단독 투여로 69명(76.7%)의 환자가 효과를 나타내었으며 이 때 사용된 Carbamazepine의 일일 용량은 평균 402.9mg이었다. 반면에 16명(17.8%)의 환자는 Carbamazepine과 다른 약물을 복합 투여하여 효과를 나타내었고 사용된 Carbamazepine 일일 용량은 평균 618.8mg이었으며 가장 많이 사용된 병용 약물은 Baclofen이었다. 나머지 5명(5.6%)의 환자는 Carbamazepine으로 효과를 얻지 못했다. 5. Carbamazepine 단독 투여에 효과가 있었던 69명 중 39명은 내원 기간 동안 지속적인 효과를 나타내었으나 30명은 Carbamazepine에 대한 효과가 감소하였거나 부작용으로 인해 복합 투약을 시행하였거나 다른 약물로 교체 또는 신경외과로 의뢰하였다. 6. 54명(60%)의 환자에서 Carbamazepine 투여 후 현기증, 졸음, 오심, 혈구 감소, 피부 발진 등의 부작용이 발생하였으나 대부분 그 정도가 미약하거나 일시적이었고 11명의 환자가 부작용으로 인해 Carbaamzepien 투약을 중단하였다.