• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1992.05a
• /
• pp.39-39
• /
• 1992

5-Hydroxytryptamine(serotonin, 5-HT)은 중추신경의 신경 전달물질로서 조울병, 불안신경증 등의 정신병태생리에 중요한 역할을 한다. Radioligand 결합실험에 의하여 5-$HT_{1A}$, 5-$HT_{1B}$, 5-$HT_{1C}$, 5-$HT_{1D}$, 5-$HT_{2}$, 5-$HT_3$의 5-HT receptor subtypes의 존재가 확인되어 있고, 그 중에서도 5-$HT_{1A}$ receptor는 중추작용 증 정 도의 조절에 관계가 깊은 raphe nuclei 및 해마에 주로 존재하여 약리학적으로는 체온강하, 혈압 강하, 과식작용, corticosterone 분비 등과 관련되어 있음이 알려져 있다. 따라서 본 수용체 agonist가 항불안약, 항우울약 또는 항고혈압약으로서의 응용이 가능해지면서 5-$HT_{1A}$ 수용체 기능의 해명 및 그 agonist의 개발이 주목받고 있는 가운데, 본 연구에 있어서, 항불안약 개발목적으로 합성된 일련의 화합물 중 1-<3-(3,4-methylene-dioxyphenoxy)propyl> 4-phenyl piperazine (DP-554)이 5-HT 수용체에 특이적이고 선택적으로 높은 친화성을 가지며, rat 해마의 막분획에서 adenylate cyclase 활성을 억제하고, 뇌내 5-HT turnover rate를 감소시키는 둥의 약리학적 작용을 나타내어, 이 화합물이 5-$HT_{1A}$ receptor agonist로서 작용함을 밝혔다. Mouse vas deferens (MVD)를 이용한 실험에서 5-$HT_{1A}$ receptor가 MVD의 교감신경 말단에 존재하여 그 neurotransmission을 억제함이 시사되었으며, 이 조직에서 또한 5-$HT_2$와 5-$HT_3$ 수용체의 존재를 확인하고 각각의 기능을 분명히 했다.

• The Korean Journal of Pharmacology
• /
• v.28 no.2
• /
• pp.137-146
• /
• 1992

The central tryptaminergic system has been shown to play an important role in the regulation of renal function: $5-HT_1$ receptor mediate diuresis and natriuresis, whereas both $5-HT_2$ and $5-HT_3$ mediate antidiuresis and antinatriuresis. Recently, $5-HT_1$ receptors are further subdivided into many subtypes, and central $5-HT_{1A}$ subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of $5-HT_{1B}$ subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective $5-HT_{1B}$ agonist in doses ranging from 8 to $750\;{\mu}g/kg$ icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with $250\;{\mu}g/kg$ icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective $5-HT_1$ blocker. Both ketanserin and MDL 72222, selective $5-HT_2$ and $5-HT_3$ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, $5-HT_{1A}$ blocker, affect the TFMPP effects. These observations suggest that central $5-HT_{1B}$ receptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.

• Proceedings of the Korean Society of Developmental Biology Conference
• /
• 2003.10a
• /
• pp.65-65
• /
• 2003

Serotonin(5-hydroxytriptamine, 5-HT)은 biogenic amlne류 신경전달물질로써, 다양한 생리조절활성을 갖고있다. 생식과 관련된 5-HT 기능으로 최근 사정 기능의 조절 가능성이 제시되었는데, 항우울제로 흔히 사용되는 selective serotonin reuptake inhibitor(SSRI) 계 약물을 장기 투여할 때 Premature ejaculation이 개선된다는 임상적인 증거들이 보고되었다. 본 연구는 수컷 흰쥐를 사용하여 생식기관, 특히 사정과 관계되는 기관들에서의 5-HT 수용체 아형들의 유전자 발현 여부와 그 조절 기작을 조사하였다. 흰쥐 수컷의 생식장기들인 고환, 부정소, 정관, 정낭에서 사정현상에 관여하리라 추정되는 세로토닌 수용체 아형들(type 1A, 1B, 2C)의 유전자 발현을 RT-PCR과 Southern blot으로 확인하였다. SSRI(sertraline)을 흰쥐에 매일 투여하는 모델(25mg/개체, 2주간)에서 1A 아형의 발현의 경우 정낭에서는 감소하였으나 정관에서는 증가하였고, 1B 아형의 발현은 두 장기에서 공히 증가하였다. 고환 제거후 testosterone(T) 보충 실험 모델을 사용한 실험에서, 정낭에서의 1A와 1B 발현은 T 보충에 의해 감소하였고, 정관에서는 큰 변화가 없었다. 한편 고환, 정낭과 정관에서의 세로토닌 수용체 아형 1A와 1B의 발현은 사춘기의 개시와 함께 증가하였다가 이후 점차 감소하는 경향을 보였다. 본 연구 결과는 사정 현상에 있어서 말초성 세로토닌 시스템이 중요한 역할을 담당할 가능성을 시사하는 것으로써, (i) 고등 포유동물에서의 사정 기작의 조절에 대한 과학적인 이해를 증진시키고, (ⅱ) 세로토닌 수용체 아형간의 특이한 발현과 작용에 대한 이해를 통해 보다 효과적인 사정 부전 치료법 개발을 시도할 수있고, (ⅲ) ontogeny와 sex steroid 의존성에 관련된 연구 시도는 노화와 관련된 사정능력의 변화와 같은 남성과학 분야로의 접목을 기할 수 있다고 사료된다.

• Korean Journal of Biological Psychiatry
• /
• v.11 no.2
• /
• pp.146-154
• /
• 2004

Objective:Attention deficit hyperactivity disorder(ADHD) is the most common childhood psychiatric disorder, affecting 3-5% of school-aged children. Although the biological basis of ADHD is unknown, family studies provide strong evidence that ADHD has a genetic basis. Recent genetic studies have suggested associations between ADHD and serotonin 1B(5HT1B) receptor gene G861C polymorphism. The aim of this study is to test for the association between ADHD and 5HT1B receptor gene G861C polymorphism in Korean population. Method:We processed DNA extraction and genotyping. 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test(TDT) and haplotype-based haplotype relative risk (HHRR). And the ADHD children were compared with 212 age and gender matched normal controls. Results:There was no statistical difference of distributions between ADHD cases and controls. We did not observe any preferential transmission of alleles of 5HT1B receptor gene G861C polymorphism in ADHD. Conclusions:Though there is the possibility of failing to detect small genetic effects, our results show no evidence of an association between ADHD and 5HT1B receptor gene G861C polymorphism in the Korean population and indicate that it is unlikely that the 5HT1B receptor is implicated in the susceptibility to ADHD.

• The Korean Journal of Pharmacology
• /
• v.20 no.2
• /
• pp.15-21
• /
• 1984

It was aimed to study the effects of ${\alpha}_2-adrenoceptor$ agonists on the sleeping time in $one{\sim}two-day-old$ chickens. Furthermore, it was also evaluated whether ${\alpha}_1-adrenoceptor$ agonist and antagonist might affect the sleeping in the chickens and discussed in relation with opiate receptor. 1) Guanabenz, clonidine, guanfacine and B-HT 933 decreased the latency of the loss of righting reflex in a dose-dependent manner, but B-HT 920 and oxymetazoline slightly prolonged it. 2) ${\alpha}_2-Adrenoceptor$ agonists produced dose·related increase in sleeping time. The potency was guanabenz>clonidine>oxymetazoline${\geq}$B-HT 933${\geq}$B-HT 920>guanfacine in this order. 3) ${\alpha}_2-Adrenoceptor$ antagonists decreased guanabenz-induced sleeping time in a dose ·dependent manner. The rank order of ${\alpha}_2-adrenoceptor$ antagonists was yohimbine>rauwolscine>piperoxan${\geq}$RX 781094. 4) Sleeping time caused by both ethanol and hexobarbital was not affected by yohimbine in chickens. 5) Methoxamine and phenylephrine showed little significant effect on the guanabenz-induced sleeping time. However, prazosin increased it. Paradoxically, corynanthine rather caused to decrease it. These results suggest that the stimulation of central ${\alpha}_2-adrenoceptor$ mediates sleeping, however it is remained uncertain in the role of central ${\alpha}_1-adrenoceptor$ in chickens. In addition, the one~two-day-old chickens may be considered as a useful, inexpensive and simple experimental model to evaluate the in vivo pharmacological action of the ${\alpha}_2-adrenoceptor$ agonist and antagonist related to sedation.

• Development and Reproduction
• /
• v.6 no.2
• /
• pp.111-115
• /
• 2002

5-Hydroxytryptamine(5-HT; serotonin) system has been implicated in the modulation of male sexual behaviors and the secretion of reproductive hormones. In human males, selective serotonin re-uptake inhibitors(SSRIs) are known to improve the major male sexual dysfunction, premature ejaculation, through the central nervous system-mediated pathways. As numerous hormone and local factors, 5-HT may have peripheral role in the regulation of male sexual function. The expression of 5-HT receptor subtypes in the target tissue, however, has not been explored yet. The present study was undertaken to test whether the 5-HT receptor subtypes are expressed in the reproductive tissues of male rat, especially in ejaculatory machinery such as seminal vesicle and vas deferens. To do this, reverse transcription-polymerase chain reaction(RT-PCR) and Southern blot analysis were employed. The transcripts for the 1A, 1B and 2C subtypes of 5-HT receptor were amplified in all the tested tissues. The present study demonstrated the expression of 5-HT receptor in the rat ejaculatory machinery, suggesting that 5-HT may play a pivotal role in the male sexual function via not only central pathway but also peripheral route. Further study on the receptor subtype-specific effect and their harmonized mode of action will be needed to establish the understanding of ejaculation mechanism and drug design.

• Korean Journal of Biological Psychiatry
• /
• v.5 no.1
• /
• pp.34-45
• /
• 1998

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide- receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent ${\mu}$-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.

• Biomolecules & Therapeutics
• /
• v.9 no.2
• /
• pp.88-95
• /
• 2001

(+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

• Korean Journal of Clinical Pharmacy
• /
• v.15 no.2
• /
• pp.160-164
• /
• 2005

수마트립탄은 뇌혈관에 분포되어 있는 5-HT1B/1D수용체에 특이적이고 선택적으로 작용하여 뇌혈관 수축 작용을 나타내어 편두통의 치료에 널리 쓰이는 약물이다. 본 연구는 수마트립탄 제제인 이미그란(50 mg tablet, GSK사)을 대조약으로 하여 시험약인 명인 제약의 수마트란 50mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 1정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 수마트립탄의 혈장 중의 농도를 정량하기 위하여 발리데이션된 HPLC/FD를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3,4, 5, 7, 9, 12시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도 곡선 하 면적$(AUC_{12hr})$ 최고 혈중 농도$(C_{max})$를 사용하였다. $AUC_{12hr}$의 평균은 $137.87ng{\cdot}ml/hr$(시험약)과 $130.12ng{\cdot}ml/hr$(대조약)으로 나타났다. $C_{max}$의 경우 각 각 29.30 ng/ml(시험약)과 29.25ng/m1(대조약)으로 관찰되었다. $AUC_{12hr}$의 경우 로그변환 한 평균치 차의 90% 신뢰구간이 log0.95-log1.24이었고, $C_{max}$의 경우 log0.90-log1.149로 계산되 어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의 약품 안전청 과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 수마트란 정 50 mg은 대조약 이미그란 정 50 mg에 대하여 생물학적으로 동등한 것으로 판정되었다.