• 제목/요약/키워드: Serotonin and dopamine receptors

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도파민과 세로토닌 운반체 및 수용체 영상을 위한 방사성리간드 (Radioligands for Imaging Dopamine and Serotonin Receptors and Transporters)

  • 지대윤
    • 대한핵의학회지
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    • 제34권3호
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    • pp.159-168
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    • 2000
  • In the 1980s, techniques to image the human subjects in a three-dimensional direction were developed. Two major techniques are SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) which allow the detector to detect a single photon or annihilation photons emitted from the subjects injected with radiopharmaceuticals. Since the latter two techniques can measure the density of receptors, enzymes and transporters in living human, it may be very important project to develop selective methods of labeling with radionuclides and to develop new radiopharmaceuticals. There has been a considerable interest in developing new compounds which specifically bind to dopamine and serotonin receptor and transporters, and it will be thus very useful to label those compounds with radionuclides in order to gain a better understanding in biochemical and pharmacological interactions in living human. This review mentions the characteristics of radioligands for the imaging of dopamine and serotonin receptors and transporters. Although significant progress has been achieved in the development of new PET and SPECT ligands for in vivo imaging of those receptors and transporters, there are continuous needs of new diagnostic radioligands.

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메스암페타민 자발섭취가 흰쥐 뇌조직 중 세로토닌 수용체에 미치는 영향 (The Effects of Self-administration of Methamphetamine on Serotonin Receptors Level in Rat Brain)

  • 박기숙;홍진태;한진이;김혜진;김용규;이종권;안광수;이선희
    • Biomolecules & Therapeutics
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    • 제9권2호
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    • pp.88-95
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    • 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.

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Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • 대한핵의학회지
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    • 제18권2호
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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Amperozide Decreases Cocaine-Induced Increase in Behavior and Immediate Early Gene Expression in the Dorsal Striatum

  • Choe, Eun-Sang;Kim, Jong-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • 제4권5호
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    • pp.361-367
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    • 2000
  • Cocaine functions as indirect dopamine and serotonin (5-hydroxytryptamine, 5HT) agonists and induces genomic and behavioral alterations in the striatum. Previously we demonstrated that ritanserin, a 5HT2/1C receptor antagonist, is not responsible for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum (see the previous paper in this issue). In this study, it was hypothesized that dopamine and 5HT2/1C receptors are required for cocaine-induced behavioral alterations and c-fos and zif268 mRNA expression. This hypothesis was addressed by infusing amperozide which antagonizes both 5HT2/1C and dopamine receptors and was analyzed using the quantitative in situ hybridization histochemistry in vivo. Systemic injection of amperozide (5 mg/kg, s.c.) significantly blocked increase in behavior, c-fos and zif268 mRNA expression induced by 15 mg/kg cocaine, i.p., in the dorsal striatum. These data suggest that dopamine and 5HT2/1C receptors are necessary for cocaine-induced behavioral alterations and immediate early gene expression in the dorsal striatum.

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지프라시돈의 효능 및 안전성 (Efficacy and Safety of Ziprasidone)

  • 유봉규
    • 한국임상약학회지
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    • 제11권2호
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    • pp.89-96
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    • 2001
  • Ziprasidone is equally effective as haloperidol in treating schizophrenia with fewer side effects and drug interactions. Ziprasidone is an atypical antipsychotic agent and works by blocking serotonin and dopamine receptors in the central nervous system, specifically 5-HT2A and D2 receptors. Low anticholinergic side-effects and low EPS would recommend the drug for use in the elderly. Ziprasidone inhibits reuptake of norepinephrine and serotonin at neurojunction sites in vitro, indicating a potential efficacy for depression and negative symptoms which often follow after exacerbation of schizophrenia. Patients with recent acute myocardial infarction and uncompensated heart failure are contraindicated to the drug due to a possibility of QT prolongation. Although ziprasidone is metabolized by cytochrome P450 3A4, there is no significant drug interaction with the drugs that induce or inhibit the isoenzyme. Ziprasidone is safe with coadministration of lithium and there has been no significant drug interaction reported with oral birth control pills.

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YKP1447, A Novel Potential Atypical Antipsychotic Agent

  • Dong, Seon-Min;Kim, Yong-Gil;Heo, Joon;Ji, Mi-Kyung;Cho, Jeong-Woo;Kwak, Byong-Sung
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권2호
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    • pp.71-78
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    • 2009
  • (S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

Risperidone의 급성 및 만성 투여가 흰쥐 뇌의 Serotonin과 Dopamine 수용체에 미치는 영향 (Effect of Acute and Chronic Treatment with Risperidone on the Serotonin and Dopamine Receptors in the Rat Brain)

  • 최윤영;손혜경;김창윤;이철;이희경;문대혁
    • 대한핵의학회지
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    • 제31권1호
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    • pp.9-18
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    • 1997
  • 목 적 : 본 연구에서는 정량적 자가방사선사진법을 이용하여 비정형 항정신병 약물의 하나인 risperidone 이 백서 뇌의 신경수용체에 어떻게 작용하는지를 알아보고자 하였다. 대상 및 방법 : 급성투여군은 백서 30마리를 6군으로 나누어 0, 0.1, 0.25, 0.5, 1, 2mg/kg의 risperidone을 복강내 투여하고 2시간후에 단두하였고, 만성투여군은 0, 0.1, 1mg/kg의 risperidone을 21일간 복강내 투여후 단두하여 정량적자가 방사선사진법으로 $5-HT_2$$D_2$ 수용체에 대한 [$^3H$]spiperone 결합을 측정함으로써, 선조체, 측좌핵, 전두엽피질 각각의 $5-HT_2$$D_2$ 수용체의 분포변화를 측정하고 투여량에 따른 수용체의 영향을 ANOVA 검정으로 분석하였다. 결 과 : 급성투여군에서 $5-HT_2$ 수용체는 전두엽 피질에서 risperidone 투여후 0.1-2mg/kg의 투여 범위전체에서 [$^3H$]spiperone 결합이 대조군에 비하여 32% 이하로 감소하여 통계적으로 유의한 차이를 보였으며, 선조체와 측좌핵의 피질하 수용체에서는 거의 결합을 보이지 않았다. $D_2$ 수용체는 risperidone 투여량의 증가에 따라 선조체와 측좌핵의 [$^3H$]spiperone 결합이 감소하였으며, 1-2mg/kg의 투여량을 준 경우에는 대조군에 비해 57% 이하로 감소하여 통계적으로 유의한 차이를 보였다. 만성투여군에서는 피질의 $5-HT_2$ 수용체가 대조군에 비하여 저용량투여군과 고용량투여군에서 각각 51%와 46%로 감소하였다. 결론 : Risperidone은 $D_2$ 수용체를 약하게 차단하며 $D_2$ 수용체에 영향을 주는 양보다 적은 양을 투여해도 $5-HT_2$ 수용체를 차단하는 효과를 보임으로써 $5-HT_2$ 수용체에 강력히 작용하는 비정형 항정신병 약물임을 알 수 있었다.

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NMDA Receptor Antagonists Enhance 5-HT2 Receptor-Mediated Behavior, Head-Twitch Response, in PCPA-Treated Mice

  • Kim, Hack-Seang;Park, In-Sook;Lim, Hwa-Kyung;Choi, Hong-Seork
    • Archives of Pharmacal Research
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    • 제22권2호
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    • pp.113-118
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    • 1999
  • Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

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