• 대한물리치료과학회지
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• 제10권1호
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• pp.65-73
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• 2003

The purpose of this study was to determine whether neuromuscular electrical stimulation(NMES), applied over the antagonist or the agonist, would alter the H reflex. Attention was focused on the roles of stimulus location. We used normal eight subjects without neuromuscular disease which were divided into 3 groups; the subjects were diveded into group of antagonist, agonist, antagonist-agonist. All groups were meted of eight subjects. Neuromuscular electrical stimulation was administered for 15 minutes. All subjects were subjected to three tests, including a pre-test, post-test and post-20 minute test. The data were analyzed by repeated measures ANOVA and paired t-test. The results were as follows; 1. H latencies were significantly increased in agonist and antagonist-agonist group (p<.01). 2. H/M intervals were significantly increased in agonist and antagonist-agonist group (p<.01). 3. H amplitudes were significantly increased in agonist (p<.001) and antagonist-agonist group (p<.01). 4. H/M ratios were significantly decreased in agonist and antagonist-agonist group (p<.01). In agonist group. H-reflex amplitudes and H/M ratios were more significantly decreased than antagonist group. Future studies will need to determine what influence NMES may have on the excitability of spinal motor neurons in people having UMN syndrome.

• 대한임상전기생리학회지
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• 제1권1호
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• pp.1-15
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• 2003

The purpose of this study was to determine the effect of neuromuscular electrical stimulation(NMES) on the alteration of spinal motor neuron excitability. In this article, I would like to experiment on a standard capacity of clinical electrophysiology, a difference in applying methods and a clinical efficiency of NMES by Nerve conduction velocity. We used normal eight subjects without neuromuscular disease and all subjects participated 3 session, which at least 1 week between session. Participants classified according to each group in Antagonist, Agonist, Antagonist-Agonist by the NMES. The test was measured continuously pre test, post-test, post 20 minute test by EMG including H reflex, F wave, motor nerve conduction velocity(MNCV). The following results were obtained; 1. H-reflex latencies and H/M intervals were significantly increased in agonist and antagonist-agonist group(p<.01). 2. H-reflex amplitudes and H/M ratios were significantly decreased in agonist and antagonist-agonist group(p<.01). In agonist group, H-reflex amplitudes and H/M ratios were more significantly decreased than antagonist group. 3. F-wave latencies were significantly increased in agonist and antagonist-agonist group(p<.01). F/M intervals were significantly increased in antagonist-agonist group(p<.01). F wave conduction velocities were significantly increased in agonist and antagonist-agonist group(p<.01) but F/M ratios were not significant. 4. MNCV were significantly decreased in agonist(p<.01). These results lead us to the conclusion that agonist and Antagonist-agonist was significantly decreased excitability of spinal motor neuron. Conversely, Antagonist does not decreased. Therefore, A further direction of this study will be to provide more evidence that NMES have an effect on excitability of spinal motor neurons in UMN syndrome.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.435-441
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• 2019

The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.

• 대한수의학회지
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• 제39권2호
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• pp.276-286
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• 1999

In the present study, to understand how gonadotropin-releasing hormone (GnRH) affects ovarian functions in superovulated rats, we examined the effects of GnRH agonist on the ovulatory response, the morphological normality and nuclear maturation of ovulated oocytes, the ovarian weight, the ovarian histology, and the circulating steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in immature rats pretreated with 30IU pregnant mare serum gonadotropin (PMSG) and supplemented with 10IU human chorionic gonadotropin(hCG). GnRH agonist was intravenously injected via jugular vein catheter every 20min for 4hrs in early follicular phase (from 6hr after PMSG) of superovulated rats. In addition, GnRH antagonist, Antide, was intravenously injected in combination with GnRH agonist to verify the effects of GnRH agonist on ovarian functions. All animals were sacrificed at 72hr after PMSG administration. The administration with GnRH agonist in early follicular phase of superovulated rats caused inhibition of ovulatory response, increased the proportion of abnormal appearing oocytes(especially, in the rats of the group treated with 500ng GnRH agonist), decreased ovarian weight and promote follicular atresia, compared to those from the rats of control regimen that were not treated with GnRH agonist. In addition, the treatment with GnRH agonist in the superovulated rat distinctly decreased serum steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in preovulatory phase. On the other hand, the inhibitory effects of GnRH agonist treatment in superovulation-pretreated rats on ovarian functions were totally reversed by the combination with GnRH antagonist, Antide. The nuclear maturation of oocytes recovered from the oviducts in immature rats treated with GnRH agonist and/or GnRH antagonist was characterized by prematurity and asynchronization in early follicular phase, which was similar to control group. The overall results of this study indicate that GnRH agonist disturbs directly ovarian function in early follicular phase of superovulated immature rats in terms of ovulatory response and morphological normality of ovulated oocytes. This concept has been further evidenced by the findings of a great decrease in ovarian weight, a marked increase in follicular and a distinct decrease circulating steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in GnRH agonist treatment regimen in early follicular phase.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.231-231
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• 1994

이 연구는 인삼 성분 약물이 도파민 수용체에 미치는 영향을 연구하기 위한 첫 단계로써 그 기본적인 assay system을 정착 시키기 위함이 목적이었다. 우리는 이 연구를 수행하기 위하여 생후 2-4 일의 쥐를 사용하여 흑질, 선조체, 해마구, nucleus accumbens등의 뇌 부위에서 신경세포 배양을 시도하였다. 흑질로 부터 배양한 신경세포들의 경우엔 면역 세포학적방법을 써서 살펴본 결과 대부분의 신경이 도파민성 신경이나 GABA성 신경들 이었다. 또한 이들 세포들의 전기 생리학적 상태를 알아보기 위하여 흑질에서 신호 전달체계가 잘 확립된 GABA 수용체의 작용을 살펴 본 결과 이 신경세포들은 GABA-A 및 GABA-B 수용체의 발현은 물론 이온 채널에 미치는 신호 전달체계를 완전히 갖추고 있었다. 도파민 수용체의 작용을 전기 생리학적으로 연구하기 위하여 배양한 신경세포에 도파민agonist를 가해서 이온 채널에 미치는 효과를 살펴 보았다. 선조체에서 배양한 신경세포들은 Dl 과 D2 agonist에 대해서 상반되는 반응을 나타냈다. 즉 Dl agonist는 선조체 신경세포를 활성화 시켰으나 D2 agonist는 선조체 신경세포들을 억제 하였다. 한편 해마구의 CAI 과 CA3 부위로 부터 배양한 신경세포에 대한 도파민 agonists의 작용은 선조체의 신경세포에 대한도파민 agonists의 작용과는 상반되는 반응 이었다. Dl agonist는 해마구로 부터 배양한 신경세포의 활성을 억제 하였으나 D2 agonist는 이들 신경세포들의 활성을 증가 시켰다. Nucleus accumbens 에서 배양한 신경세포들은 도파민에 의해서 그 활성이 억제 되었다. 이러한 결과로 미루어 봐서 같은 도파민 수용체라도 분포되어 있는 조직에 따라서 신호전달 에 관여 하고 있는 C-단백이나 이차 전령물질이 달라서 신경세포에 대한 작용이 다르든지. 약리학적으로는 구분되지 않으나 뇌의 조직에 따라서 분포가 다른 도파민 수용체의 아그룹이 존재 한다고 생각된다.

• 비만대사연구학술지
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• 제1권1호
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• pp.4-13
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• 2022

Currently, pharmacotherapy is becoming essential for obesity, owing to its expanding and increasing epidemiology. In this review, novel peptide-based drugs of four classes are covered: GLP-1 receptor agonist, GIP/GLP-1 receptor dual agonist, glucagon/GLP-1 receptor dual agonist, and a combination of amylin receptor agonist/GLP-1 receptor agonist. Semaglutide is a next-generation GLP-1 receptor agonist with a longer duration and stronger weight and glucose reduction effects than liraglutide and dulaglutide. In the STEP1 trial, semaglutide 2.4 mg reduced body weight by approximately 15% in people with obesity with similar or milder adverse events than liraglutide 3.0 mg. Tirzepatide, a GIP/GLP-1 receptor dual agonist, also has a long duration and strong weight- and glucose-lowering effect. According to SURPASS-2, 3, and 4, in patients with BMI≥25 kg/m² and type 2 diabetes mellitus (T2DM), tirzepatide 15 mg reduced the initial body weight by >13%. Cotadutide, a glucagon/GLP-1 receptor dual agonist, showed weaker weight-lowering effects than semaglutide and tirzepatide, while it was comparable to that of liraglutide in a phase 2 clinical trial for non-alcoholic fatty liver disease in patients with BMI≥25 kg/m² and T2DM. Additionally, its effect on the liver was noticeable. The long-acting amylin receptor agonist cargrilintide combined with semaglutide can be another effective option for obesity treatment. Even in a small phase 1 trial with a short study period of 20 weeks, cargrilintide 2.4 mg/semaglutide 2.4 mg reduced by 17% of initial body weight in people with BMI 27-39.9 kg/m². In coming several years, semaglutide, tirzepatide, and cargrilintide/semaglutide will become available for obesity treatment in Korea.

• 한국수정란이식학회지
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• 제13권3호
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• pp.261-275
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• 1998

본 연구에서는 GnRH가 과배란 처치된 래트의 초기 난포기와 후기 난포기에서 난소기능에 어떠한 영향을 미치는지를 이해하기 위해서, 30IU PMSG와 10IU hCG로 전처치된 미성숙 래트에 있어서 배란반응, 배란 난자의 형태학적 이상 유무 및 핵 성숙도, 난소 중량, 난소의 조직학적인 변화 및 혈중 스테로이드 호르몬 (17$\beta$-estradiol, progesterone 및 testosterone) 농도에 대하여 GnRH agonist의 효과를 검사하였다. GnRH agonist는 PMSG 전처치 후 초기 난포기 (PMSG 투여 후 6시간부터) 또는 후기 난포기(PMSG 투여 후 54시간부터)에 4시간 동안 20분 간격으로 경정맥 카테타를 통해 혈관내로 투여하였다. 각 실험동물은 혈중 스테로이드 호르몬의 변화를 측정하기 위하여 PMSG 투여 후 54시간, 72시간에 혈액을 채취하고 72시간에 희생시켰다. PMSG로 전처치한 미성숙 래트의 초기 난포기에 GnRH agonist의 투여는 GnRH agonist를 투여하지 않은 군(대조군)에 비해 과배란 억제, 형태학적 비정상 배란난자의 증가, 난소 중량의 감소, 난포폐쇄의 증가 및 혈중 스테로이드 호르몬의 농도 감소가 보였다. 한편 후기 난포기에 GnRH agonist의 투여는 대조군에서의 반응과 전반적으로 유사하였다. 이상의 결과, PMSG 및 hCG 처치로 과배란된 래트의 초기 난포기에 GnRH agonist의 투여는 난소기능을 전반적으로 억제하지만, 후기 난포기에 GnRH agonist의 투여는 난소기능에 영향을 미치지 않았다.

• Clinical and Experimental Reproductive Medicine
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• 제34권2호
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• pp.125-131
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• 2007

목 적: 난소 반응이 저하된 환자에서 GnRH agonist flare up protocol과 GnRH antagonist protocol의 효용성을 비교하고자 하였다. 연구방법: 2003년 1월부터 2005년 8월까지 체외수정시술을 받은 환자들 가운데 이전의 체외수정시술 주기에서 5개 이하의 난자가 채취되고 기저 FSH 농도가 12 mIU/ml 이상인 총 144명 가운데 73명은 GnRH agonist flare up요법을 사용하였고 71명은 GnRH antagonist 요법을 사용하였다. 양군간에 주기의 취소율, 채취된 난자수, 양질의 수정란의 수, 착상율, 임신율, 출산율을 비교하였다. 결 과: 각 군간에 나이는 평균 37.4세와 38.1세로 antagonist group에서 높았으나 통계학적 유의성은 없었다. 그 외에 기저 FSH 농도와 이전 주기의 취소율도 통계학적 유의성은 없었다. GnRH agonist flare up 주기와 GnRH antagonist 주기에서 취소율은 각각 30.1%, 53.5%로 GnRH antagonist protocol에서 유의 있게 높게 나타났다. 채취된 난자수도 각각 4.18개와 2.16개로 차이를 보였으며 난소 과자극 기간은 각각 10.5일과 9.2일로 antagonist protocol에서 약간 낮은 모습을 보였다. 최고 혈중 E$_2$의 농도와 good embryo 개수도 GnRH agonist flare up요법에서 유의 있게 높게 나타났다. 각 군에서의 착상율, 이식 주기당 임신율, 이식 주기당 출생율은 GnRH agonist flare up요법에서 약간 높은 경향을 보이기는 하였으나 통계학적인 유의성은 없었다. 결 론: 두 군간의 비교에서 GnRH agonist flare up 요법이 시작 주기당 임신율, 출산율에서 높은 경향을 보였으나 통계학적 의의는 없었다. 하지만 난소기능이 저하된 환자에서 난자의 채취 개수는 GnRH agonist flare up 요법이 GnRH antagonist를 사용한 주기보다 의의있게 높게 나타났다. 이러한 연구 결과로 볼 때 저 반응군에 있어서 GnRH antagonist flare up요법이 저 반응군에 있어 향상된 난소 반응을 기대할 가능성이 높을 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제4권2호
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• pp.196-201
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• 1996

The N-methyl-D-aspartate (NMDA) receptor-ion channel complex is activated by the simultaneous presence of L-glutamate and glycine, allowing the binding of MK-801 to the phencyclidine (PCP) site of the receptor. The $[^3H]$MK-801 binding assay system was established for determination of pharmacological functions of test compounds acting at the glycine site of the receptor. The binding in the presence of 0.1 $\mu$M L-glutamate was increased by an agonist (glycine) in a dose-dependent fashion, while decreased by either partial agonist (R-(+)-HA-966) or antagonist (5,7-dichlorokynurenic acid: 5,7-DCKA). To distinguish partial agonism from antagonism, various concentrations of 7-chlorokynurenic acid (7-CKA) were added in the assay to eliminate the interference of the endogenous glycine present in the membrane preparations. The bindings in the presence of L-glutamate (0.1$\muM$) and 7-CKA (1, 5, or 10$\muM$) were increased by R-(+)-HA-966. Being a weak partial agonist, the extent of potentiation was much less than that by the agonist. These binding profiles were clearly distinguishable from those by the antagonist, 5,7-DCKA, which exhibited no intrinsic activity. The binding assays established in the present study are a useful system to classify ligands acting at the glycine site of the NMDA receptor by their pharmacological functions.

• Clinical and Experimental Reproductive Medicine
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• 제30권1호
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• pp.95-103
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• 2003

Objective : To assess and compare the clinical outcomes between GnRH agonist long protocol and GnRH antagonist short protocol in oocyte donation program. Materials and Methods: Of total 18 oocyte donation cycles, controlled ovarian hyperstimulation (COH) were performed with GnRH agonist long protocol and GnRH antagonist short protocol in initial 9 cycles and later 9 cycles, respectively. Oral estradiol valerate and progesterone in oil we re administrated to all recipients for endometrial preparation. Oral estradiol administration was started from donor cycle day 1 after full shut down of gonadal axis with GnRH agonist in patients with ovarian function. Progesterone was injected from oocyte retrieval day of donor initially, then continuously till pregnancy 12 weeks if pregnancy was ongoing. We compared the parameters of clinical outcomes, such as number of the retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, COH duration, total gonadotropin dose for COH between GnRH agonist long protocol group and GnRH antagonist group. Statistical analysis was performed using Mann-Whitney test, p<0.05 was considered as statistically significant. Results: The number of retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate were $14.89{\pm}7.83$, 81%, 64%, 78%, 31%, 78%, respectively in GnRHa long protocol group and $11.22{\pm}8.50$, 79%, 64%, 67%, 34%, 56%, respectively in GnRH antagonist group. There was no significant differences in parameters of clinical outcomes between 2 groups (all p value >0.05). Duration and total gonadotropin dose for COH were $10.94{\pm}1.70$ days and $43.78{\pm}6.8$ vials in 18 cycles, $12.00{\pm}1.73$ days and $48.00{\pm}6.93$ vials in agonist group, $9.88{\pm}0.78$ days and $39.55{\pm}3.13$ vials in antagonist group, respectively. In GnRH agonist long protocol group, significantly longer duration and higher gonadotropin dose for COH were needed (p=0.012). Conclusion: In oocyte donation program, clinical outcomes from controlled ovarian hyperstimulation with GnRH antagonist were comparable to those from GnRH agonist long protocol group, so controlled ovarian hyperstimulation with GnRH antagonist may be effective as GnRH agonist long protocol. At least there may not be harmful effects of GnRH antagonist on oocyte development and quality.