• Archives of Pharmacal Research
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• v.29 no.5
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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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• v.30 no.3
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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.

• YAKHAK HOEJI
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• v.58 no.5
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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.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.13 no.2
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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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• v.14 no.2
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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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• v.40 no.3
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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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• v.9 no.2
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• pp.359-381
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• 1992

This study was designed to investigate the effect of diazepam on the spontaneous contraction and oxytocin induced contraction of the isolated rat uterus. Female rat(Sprague-Dawley) pretreated with oophorectomy and 4 days administration of estrogen, weighing about 200 g, was sacrificed by cervical dislocation, and the uteruses were isolated. A longitudinal muscle strip was placed in temperature controlled($37^{\circ}C$) muscle chamber containing Locke's solution and myographied isometrically. Diazepam inhibited the spontaneous contraction and oxytocin induced contraction of the isolated rat uterus in a concentration-dependent manner. GABA, muscimol, a GABA A receptor agonist, bicuculline, a competitive GAGA A receptor antagonist, picrotoxin, a non competitive GABA A receptor antagonist, baclofen, a GABA B receptor agonist, and delta-aminovaleric acid, a GABA B receptor antagonist, did not affect on the spontaneous and oxytocin induced contraction of the isolated rat uterus. The inhibitory actions of diazepam on the spontaneous and oxytocin induced contraction were not affected by all the GABA receptor agonists and antagonists, but exceptionally potentiated by bicuculline. This potentiation-effect by bicuculline was not antagonized by muscimol. In normal calcium PSS, addition of calcium restored the spontaneous contraction preinhibited by diazepam and recovered the contractile of oxytocin preinhibited by diazepam. A23187, a calcium inophore, enhanced the restoration of both the spontaneous and oxytocin induced contraction by addition of calcium. In calcium-free PSS, diazepam suppressed the restoration of spontaneous motility by addition of calcium but allowed the recovery of spontaneous motility to a considerable extent. Diazepam could not inhibit some development of contractility by oxytocin in calcium-free PSS, but inhibited the increase in contractility by subsequent addition of calcium. These results suggest that the inhibitory action of diazepam on the rat uterine motility does not depend on or related to GABA receptors and that diazepam inhibits the extracellular calcium influx to suppress the spontaneous and oxytocin induced contractilities.

• Journal of Oral Medicine and Pain
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• v.34 no.2
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• pp.207-216
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• 2009

Trigeminal neuralgia is defined "a sudden, usually unilateral, severe, brief, stabbing, recurrent pain in the distribution of one or more branches of the fifth cranial nerve". The initial treatment of choice for trigeminal neuralgia is medical therapy. In patients with medically intractable pain or intolerable medication side effects, invasive therapeutic approaches are often necessary. Based on the amount of evidence and estimated efficacy, carbamazepine is the drug of choice in the management of trigeminal neuralgia. In case of insufficient or no response to carbamazepine, second-line drugs can be added. In this study, the author tried to review and analyzed the cases of 90 patients whom had visited for treatment of trigeminal neuralgia at the Department of Oral Medicine, Kyungpook National University Hospital from 2003 to 2008. The results were as follows: 1. Trigeminal neuralgia was significantly more common with advancing age, and nearly twice as common in women than men (ratio of 2.1:1) 2. The maxillary branch of the trigeminal nerve involved most often (51.1%), and the right side of the face is affected more commonly than the left (ratio of 2.9:1). 3. 85(94.4%) patients had experiences visiting medical or dental specialties before being referred to the Department of Oral Medicine. 4. 40(44.4%) patients with trigeminal neuralgia had systemic diseases. 5. Treatment with carbamazepine monotherapy was satisfactory initially in 69(76.7%) the patients, and the mean daily dose of carbamazepine was 402.9mg. On the other hand, 16(17.8%) patients expressed effectiveness after combination therapy of carbamazepine and other drugs. 6. Of the 69 patients who had a good initial response to carbamazepine monotherapy, 18 patients became resistant, so that combination therapy of carbamazepine and other drugs were necessary. 7. 54(60%) patients developed side effects such as dizziness, drowsiness, nausea, vomiting, blood dyscrasias, skin rash and constipation, and 11 of the patients decided to stop tmedicaion due to side effects.