알콜리즘에서 Buspirone에 대한 Cortisol과 Prolactin 반응

심주철,이정구,김정익,이유철,김영훈 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.2

연구목적: 본 연구는 buspirone에 대한 cortisol과 prolactin 반응을 통해 알콜리즘에서 5-HT1A 수용체기능을 조사하고자 하였다. 방법: 알콜리즘 환자군은 DSM-IV의 알콜리즘 진단기준에 부합되고 금주기간이 최소 3개월 이상이며 우울 및 불안증상이 없는, 한 정신병원 알콜 센터에 입원한 22명의 남자 환자였다. 대조군은 정상성인 남자 15명이었다. 이들에게 오전 9시에 5-HT□ 효현제인 buspirone 30mg을 경구 투여한 후 0, 30 , 60, 90, 120, 150분의 혈청 cortisol과 prolatine 농도를 측정한다. 결과: 환자군과 대조군간에 cortisol 기저치에는 유의한 차이가 없었다. Buspirone 투여 후 혈청 cortisol 농도는 정상대조군에서는 기저치에 비해 유의한 증가를 보였으나(p<0.01) 환자군에서는 유의환 증가가 없었다. 혈중 cortisol 농도는 buspiron 투여 60분 이후부터 환자군에서 정상 대조군에 비해 유의하게 저하되어 있었다(p<0.05). Buspirone에 대한 혈청 prolactin 반응은 환자군과 정상대조군간에 유의한 차이가 없었다. 결론: Buspirone 투여 후 둔마된 혈청 cortisol 반응을 통해 알콜리즘에 5-HT1A 수용체 반응성이 둔마되어 있음을 확인할 수 있었다. Objectives: The purpose of this study was to evaluate the prolactin and cortisol responses to 5-HT1A receptor activation by buspirone in alcoholics. Methods: The subjects were twenty two male alcoholic patients meeting the DSM-IV criteria for alcohol dependency and abstaining for more than 3 months. Patients were free from overt anxiety and depressive symptoms. Controls were fifteen male normal volunteers, with no psychiatric and medical illness. Blood samples for the measurement of serum cortisol and prolactin levels were drawn 0, 30, 60, 90, 120, 150 minutes after oral administration of 30mg buspirone hydrochloride at 9:00a.m. Results: The baseline cortisol levels were not significantly different between alcoholics and controls. Serum cortisol levels of controls after buspirone administration were significantly increased over time(p<0.01), but those of alcoholics did not increased. After 60 minutes following buspirone administration, cortisol levels were significantly lower in alcoholics than in contrlos(p<0.05). Prolactin responses to buspirone were not significantly different between the two groups. Conclusions: Our results suggested that 5-HT1A receptor function is decreased in alcoholic patients.

Buspirone-induced Prolaction 분비와 5-HT_1A 수용체: Pindolol 전처치 효과

이홍식(Hong Shick Lee),J. Frank Nash,Herbert Y. Meltzer 대한약리학회 1992 대한약리학잡지 Vol.28 No.1

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 DopaminE₂ 수용체 antagonist 성질 뿐 아니라 5-HT_1A partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 5-HT_1A 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 5-HT_1A 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다. The effect of the nonbenzodiazepine anxiolytic, buspirone (Buspar^R), a serotonin (5-HT)_1A partial agonist, which also has dopamine (DA)₂ receptor antagonist properties, on prolactin and cortisol secretion was examined in eight normal male volunteers. The oral administration of buspirone (30 mg) significantly increased plasma prolactin concentrations but did not significantly increase plasma cortisol concentrations in this study. The oral administration of pindolol (30mg), a beta adrenoceptor antagonist which is also a 5-HT_1A receptor antagonist, had no significant effect on basal prolactin or cortisol levels. Moreover, pretreatment with pindolol did not significantly inhibit the buspirone-induced increase in prolactin secretion. These preliminary data are suggestive that buspirone-induced prolactin secretion is not mediated via 5-HT_1A receptor activation.

Buspirone-induced Prolactin Secretion in Man is Not $5-HT_{1A}$ Receptor Mediated: Effect of Pindolol Pretreatment

Lee, Hong-Shick,Nash, J. Frank,Meltzer, Herbert Y. The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.1

Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 $Dopamine_2$ 수용체 antagonist 성질 뿐 아니라 $5-HT_{1A}$ partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 $5-HT_{1A}$ 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 $5-HT_{1A}$ 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다. The effect of the nonbenzodiazepine anxiolytic, buspirone $(Buspar^R)$, a serotonin $(5-HT)_{1A}$ partial agonist, which also has dopamine $(DA)_2$ receptor antagonist properties, on prolactin and cortisol secretion was examined in eight normal male volunteers. The oral administration of buspirone (30 mg) significantly increased plasma prolactin concentrations but did not significantly increase plasma cortisol concentrations in this study. The oral administration of pindolol (30 mg), a beta adrenoceptor antagonist which is also a $5-HT_{1A}$ receptor antagonist, had no significant effect on basal prolactin or cortisol levels. Moreover, pretreatment with pindolol did not significantly inhibit the buspirone-induced increase in prolactin secretion. These preliminary data are suggestive that buspirone-induced prolactin secretion is not mediated via $5-HT_{1A}$ receptor activation.

Protective effects of maternal buspirone treatment on serotonin reuptake sites in ethanol-exposed offspring

Kim, Jung-Ae,Druse, Mary J. 영남대학교 약품개발연구소 1997 영남대학교 약품개발연구소 연구업적집 Vol.7 No.-

Previous work in this laboratory demonstrated that in utero ethanol exposure is associated with abnormal development of the serotonergic system. Specific abnormalities included deficiencies of serotonin (5-HT) and its metabolites, and cortical 5-HT reuptake sites. The concentration of 5-HT_(LA) receptors was also altered. The serotonin deficit was detected in the fetal ethanol-exposed brain, at an age when 5-HT would normally function as an essential trophic factor. Thus, it was hypothesized that the early 5-HT ethanol-associated deficit of an essential trophic factor (e.g. 5-HT) could contribute to subsequent developmental abnormalities in serotonergic neurons. In the present investigation we used quantitative autoradiography (QAR) to more fully characterize the developmental abnormalities in 5-HT reuptake sites in developing offspring of ethanol-fed rats. In addition, we attempted to overcome the potential negative impact of the ethanol-associated deficit of fetal 5-HT, by administering a 5-HT₁_(A) agonist, buspirone, to pregnant rats. These investigations demonstrated that postnatal (PN) 19 and/or 35 day ethanol-exposed offspring had a significant decrease in [³H]citalopram binding to 5-HT reuptake sites in the frontal cortex, parietal cortex. lateral hypothalamous, substantia nigra, medial septum, and striatum. In contrast, [³H ]citalopram binding was increased in the dorsal raphe on PN5 and in the median raphe on PN19. No significant ethanol-associated changes were detected in the hippocampus CA3 region or in the amygdala. When [³H]citalopram binding was compared in the offspring of saline- and buspirone-treated dams, it appeared that maternal treatment with buspirone prevented or reersed most of the ehanol-associated developmental abnormalities in 5-HT reuptake sites. Buspirone prevented the decline in binding of [³H ]citalopram in the frontal cortex, lateral hypothalamus, substantia nigra and medial septum. Similary, buspirone treatment preented the ethanol-associated increase in binding in the dorsal and median raphe. Additional experiments are needed to elucidate the impact of maternal buspirone treatrment on the development of other neurotransmitter systems in offspring.

Efficacy of the 5-HT_1A Agonist, Buspirone Hydrochloride, in Migraineurs With Anxiety: A Randomized, Prospective, Parallel Group, Double-Blind, Placebo-Controlled Study

Lee, Soon-Tae,Park, Jong-Ha,Kim, Manho American Association for the Study of Headache 2005 Headache Vol.45 No.8

<P>ObjectiveTo examine the efficacy of buspirone, a 5-HT<SUB>1A</SUB> agonist, for migraine combined with anxiety disorder.</P><P>BackgroundModulation of the 5-hydroxytryptamine (5-HT) system is used for the neuropharmacology of migraine treatment; however, the involvement of the 5-HT<SUB>1A</SUB> system in migraine is not fully understood.</P><P>MethodsSeventy-four outpatients aged 20 to 70 years (mean, 46.4; SD, 12.8) were analyzed. All subjects were diagnosed to have migraine according to the International Headache Society criteria and anxiety disorder according to DSM-IV. Subjects were randomly assigned to treatment with either buspirone (10 mg/day) or placebo for 6 weeks. Efficacy variables included changes in headache frequency, headache intensity, Hamilton Anxiety Rating Scale (HAM-A), Headache Self-Efficacy Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between the headache improvement and the anxiolytic effect was analyzed.</P><P>ResultsHeadache frequency showed a 43.3% reduction in the buspirone-treated group, but by only 10.3% in the placebo group. HAM-A and HDI were also significantly more lowered in buspirone-treated patients than in placebo-treated patients. However, headache intensity and HMSE score were unchanged. Correlation analysis of the relation between headache frequency reduction and HAM-A improvement, revealed no significant association.</P><P>ConclusionsIn this study, buspirone showed a prophylactic effect in migraine with anxiety disorder, which was not secondary to its anxiolytic effect. This suggests that the agonistic action for 5-HT<SUB>1A</SUB> can be directly effective in migraine prophylaxis. However, more long-term study is warranted before concluding the efficacy.</P>

Efficacy of Buspirone Augmentation of Escitalopram in Patients with Major Depressive Disorder with and without Atypical Features: A Randomized, 8 Week, Multicenter, Open-Label Clinical Trial

Cheolmin Shin,Young-Hoon Ko,Se-Hoon Shim,Ji Sun Kim,Kyoung-Sae Na,Sang-Woo Hahn,Seung-Hwan Lee 대한신경정신의학회 2020 PSYCHIATRY INVESTIGATION Vol.17 No.8

Objective This study investigated the treatment response and cognitive enhancement effects of buspirone augmentation of escitalopram in patients with major depressive disorder (MDD), according to atypical feature subtypes of MDD. Methods An 8 week, randomized, parallel-controlled, open-label study was conducted. The Columbia Atypical Depression Diagnostic Scale was administered to evaluate atypical features. Patients were assigned randomly to the buspirone augmentation or non-buspirone groups. Symptom severity and cognitive function were evaluated using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Beck Anxiety Inventory, digit span test, word fluency test, and Trail Making Tests A and B. Results A total of 89 patients were recruited. There were no significant differences in the measures between the groups; however, among the MDD patients without atypical features, the digit span and word fluency tests were improved by treatment. In the MDD patients without atypical features, the buspirone augmentation group showed a significant improvement on the digit span test compared to the non-buspirone group. Conclusion Buspirone augmentation did not demonstrate significant benefits in MDD patients; however, buspirone augmentation showed greater efficacy for the improvement of cognitive function in MDD patients without atypical features. Our study suggests that atypical features are an important factor for cognitive enhancement in buspirone augmentation treatment in patients with MDD.

Effects of Maternal Ethanol Consumption and Buspirone Treatment on 5-HT_(1A) and 5-HT_(2A) Receptors in Offspring

Kim, Jung-Ae,Gilespie, Roberta A.,Druse, Mary J. 영남대학교 약품개발연구소 1998 영남대학교 약품개발연구소 연구업적집 Vol.8 No.-

In utero ethanol exposure results in a decreased concentration of serotonin (5-HT) in brain regions containing the cell bodies of 5-HT neurons and their cortical projections. The concentration of 5-HT reuptake sites is also reduced in several brain areas. The present study extended prior work by evaluating the effects of chronic maternal ethanol consumption and maternal buspirone treatment on 5-HT_(1A) and 5-HT_(2A) receptors in mutiple brain areas of offspring. Receptors were quantitated early in postnatal development and at an age when the 5-HT networks are normally well-established. Because fetal 5-HT functions as an essential neurotrophic factor, these studies also determined whether treatment of pregnant rats with buspirone, a 5-HT_(1A) agonist, could overcome the effects of the fetal 5-HT deficit and prevent ethanol-associated receptor abnormalities. The results demonstrated that in utero ethanol exposure significantly alters the binding of 0.1 nM [³H]-8-hydroxy-dipropylaminotetralin to 5-HT_(1A) receptors in developing animals. Ethanol impaired the development of 5-HT_(1A) receptors in the frontal cortex, parietal cortex, and lateral septum; these receptors did not undergo the normal developmental increase between postnatal days 19 and 35. The dentate gyrus was also sensitive to the effects of in utero ethanol exposure. 5-HT_(1A) receptors were increased in this region at 19 days. Maternal buspirone treatment prevented the ethanol-associated abnormalities in 5-HT_(1A) receptors in the dentate gyrus, frontal cortex, and lateral septum. Neither maternal ethanol consumption nor buspirone treatment altered the binding of 2 nM [³H]ketanserin to 5-HT_(2A) receptors in the ventral dentate gyrus,dorsal raphe, parietal and frontal cortexes, striatum, substantis nigra, or nucleus accumbens.

Formulation and characterization of ternary complex of sublingual film of buspirone hydrochloride

Renuka Mishra,Arun Sharma,Tejal Mehta,Mukesh Gohel 한국약제학회 2015 Journal of Pharmaceutical Investigation Vol.45 No.4

Taste masked sublingual film of buspirone hydrochloride (BH) was developed with the objectives of taste masking, fast disintegration, increased dissolution and better patient compliance. The film was formulated using Polyox WSRN-10, polyvinyl pyrolidone (PVP) K-30 and propylene glycol as a plasticizer. Taste masking was obtained by ternary complexation between BH, β-cyclodextrin and PVP K-30. Optimized batch contained 3 % w/v of Polyox WSR N-10, 2 % w/v PVP K-30 and propylene glycol (20 % weight of Polyox WSR N-10). The optimized formulation also contained BH: β-CD (1:1.5 molar ratio), BH: sucralose (1:0.5 ratio) and 0.15 ml orange flavour. This batch was evaluated for % elongation, tensile strength, in vitro disintegration time and in vitro dissolution studies. In-vitro permeation studies employing rabbit sublingual mucosa, indicated higher drug permeability at the ventral surface than at the bottom surface of the mouth. In-vivo absorption studies in rabbits revealed that 50.27 ± 5.24 % of BH was absorbed sublingually from film within 5 min. The kinetics of in vivo drug absorbed from sublingual film in human volunteers indicated that there is no significant difference between ex vivo and in vivo data obtained for the drug absorption. The formulation, subjected to stability studies at 25 ˚C/60 % RH for 2 months, showed good stability indicating suitable packaging and storage conditions.

주의력결핍-과잉행동장애 치료 시 비중추신경흥분제 사용의 최신지견

반건호 ( Geon Ho Bahn ),이서경 ( Seo Kyung Lee ),김봉수 ( Bong Soo Kim ) 경희대학교 경희의료원 2007 慶熙醫學 Vol.23 No.2