복막투석 환자에서 발생한 Baclofen 뇌증 1예

김은혜 ( Eun Hye Kim ),김번 ( Bun Kim ),이수진 ( Su Jin Lee ),김민형 ( Min Hyung Kim ),강신욱 ( Shin Wook Kang ),최규헌 ( Kyu Hyun Chio ),유태현 ( Tae Hyun Yoo ) 대한신장학회 2011 Kidney Research and Clinical Practice Vol.30 No.2

Baclofen (β-4-chlorophenyl-γ-aminobutyric acid), a gamma-aminobutyric acid (GABA) derivative, is commonly used for relief of spinal-origin spasm or pain. Baclofen is eliminated predominantly by the kidneys, putting patients with impaired renal function at particular risk for baclofen accumulation. The authors report on a case of baclofen-induced encephalopathy in a patient on continuous ambulatory peritoneal dialysis (CAPD). A 56 year old patient with ESRD on CAPD was admitted due to stuporous mental status after baclofen treatment. Brain imaging showed no specific abnormality. After intensive treatment of CAPD for 3 days, neurologic abnormality was completely recovered. Baclofen should not be recommended for patients with renal dysfunction. Although the best-known treatment choice for baclofen toxicity is hemodialysis, intensive CAPD can also be considered as an option for treatment of baclofen toxicity.

Warfarin과 Baclofen 간의 약물 상호 작용의 검증

고현윤,박재홍,신용범 大韓再活醫學會 1999 Annals of Rehabilitation Medicine Vol.23 No.6

Baclofen Abuse due to Its Hypomanic Effect in Patients with Alcohol Dependence and Comorbid Major Depressive Disorder

Soumitra Ghosh,Dhrubajyoti Bhuyan 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.2

Baclofen is a gamma-aminobutyric acid type B receptor agonist used as an anti-craving agent for treatment of alcohol dependence. It has gained popularity in the recent times because it is well tolerated even in patients with hepatic impairments. Herein we are summarizing the latest literature about baclofen induced hypomania and are reporting a case of baclofen abuse because of its mood elevating property in a patient of alcohol dependence with comorbid major depressive disorder. Literature review and case study of a 36-year-old male with alcohol dependence with comorbid major depressive disorder was prescribed with tablet baclofen as an anti-craving agent along with antidepressant medicines. The patients who did not improve with conventional antidepressant therapy started feeling better in terms of his mood symptoms on taking tablet baclofen. Owing to the mood elevating property he started abusing baclofen. Despite its safety profile in hepatic impairment, one must be very cautious in prescribing baclofen because of its mood altering property which may account for its abuse potentiality.

Warfarin과 Baclofen 간의 약물 상호 작용 가능성

고현윤,박재흥,김훈 大韓再活醫學會 1998 Annals of Rehabilitation Medicine Vol.22 No.3

Baclofen-induced Changes in the Resting Brain Modulate Smoking Cue Reactivity: A Double-blind Placebo-controlled Functional Magnetic Resonance Imaging Study in Cigarette Smokers

Ariel Ketcherside,Kanchana Jagannathan,Sudipto Dolui,Nathan Hager,Nathaniel Spilka,Chaela Nutor,Hengyi Rao,Teresa Franklin,Reagan Wetherill 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.2

Objective: Smoking cue-(SC) elicited craving can lead to relapse in SC-vulnerable individuals. Thus, identifying treatments that target SC-elicited craving is a top research priority. Reduced drug cue neural activity is associated with recovery and is marked by a profile of greater tonic (resting) activation in executive control regions, and increased connectivity between executive and salience regions. Evidence suggests the GABA-B agonist baclofen can reduce drug cue-elicited neural activity, potentially through its actions on the resting brain. Based on the literature, we hypothesize that baclofen’s effects in the resting brain can predict its effects during SC exposure. Methods: In this longitudinal, double blind, placebo-controlled neuropharmacological study 43 non-abstinent, sated treatment-seeking cigarette smokers (63% male) participated in an fMRI resting-state scan and a SC-reactivity task prior to (T1) and 3 weeks following randomization (T2; baclofen: 80 mg/day; n = 21). Subjective craving reports were acquired before and after SC exposure to explicitly examine SC-induced craving. Results: Whole-brain full-factorial analysis revealed a group-by-time interaction with greater resting brain activation of the right dorsolateral prefrontal cortex (dlPFC) at T2 in the baclofen group (BAC) (pFWEcorr = 0.02), which was associated with reduced neural responses to SCs in key cue-reactive brain regions; the anterior ventral insula and ventromedial prefrontal cortex (pFWEcorr < 0.01). BAC, but not the placebo group reported decreased SC-elicited craving (p = 0.02). Conclusion: Results suggest that baclofen mitigates the reward response to SCs through an increase in tonic activation of the dlPFC, an executive control region. Through these mechanisms, baclofen may offer SC-vulnerable smokers protection from SC-induced relapse.

혈액투석 환자에서 Baclofen 뇌증

최문영 ( Choe Mun Yeong ),송현주 ( Song Hyeon Ju ),김미연 ( Kim Mi Yeon ),이영숙 ( Lee Yeong Sug ),김승정 ( Kim Seung Jeong ),최규복 ( Choe Gyu Bog ),윤견일 ( Yun Gyeon Il ),강덕희 ( Kang Deog Hui ),박기덕 ( Park Gi Deog ) 대한신장학회 2004 Kidney Research and Clinical Practice Vol.23 No.2

Baclofen, a derivative of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is used for the treatment of muscle spasm, intractable hiccups and multiple sclerosis. It is mostly excreted by glomerular filtration with a clearance that is proportional to creatinine clearance. Early hemodialysis is a treatment of the choice for baclofen-induced neurologic complication in renal failure patients. We experienced a 57-year-old hemodialysis patient with right arm muscle spasm who developed baclofen-associated encephalopathy by a single dose of oral baclofen (10 mg). He admitted to the hospital with the symptom of stuporous mental status with no specific focal neurologic signs. Brain CT imaging and blood biochemistry showed no specific abnormality. EEG revealed the typical metabolic encephalopathy findings, such as triphasic wave and frontal lobe syndrome with delta wave. After daily hemodialysis for 3 days, there was a complete recovery of an altered mentality. After one month later, the follow-up EEG showed normal finding with the resolution of abnormal waves. We report this case with a review of relevant literature. Baclofen should be used carefully, and rather recommended not to be administered in patients with renal failure. (Korean J Nephrol 2004;23(2):353-357)

뇌실내 Calcitonin 투여로 인한 위산분비 억제에 대한 뇌내 신경전달체의 역할

장우익(Woo Ick Jang),이동기(Dong Ki Lee),권상옥(Sang Ok Kwon),고창만(Chang Mann Ko),현재헌(Jae Hun Hyun),김상태(Sang Tae Kim),이상인(Sang In Lee),최흥재(Heung Jai Choi),김경환(Kyung Hwan Kim) 대한내과학회 1991 대한내과학회지 Vol.40 No.5

N/A Peptides that are common to the brain and gut are thought to play intermediary roles as neurotransmitters or neuromodulators in the regulation of gut function. Calcitonin is a polypeptide hormone of 32 amino acid residues. Recently, much evidence has been accumulated to suggest that calcitonin may inhibit gastric acid secretion by a central action, but the neurohumoral pathways mediating the antisecretory effects of calcitonin in rats are not well elucidated. In the present study, using a gastric perfusion technique, the effects of ICV administration of calcitonin on gastric acid secretion stimulated by baclofen were investigated in rats. We also investigated whether the serotonergic system is involved in calcitonin's effect of gastric acid secretion. The results obtained were as follows: 1) ICV administration of baclofen stimulated gastric acid secretion in a dose-dependent manner. Central administration of baclofen was approximately 200-400 times more sensitive than subcutaneous administration. 2) Baclofen-induced gastric acid secretion was partially suppressed by bilateral vagotomy. 3) Gastric acid secretion stimulated by baclofen was markedly suppressed by ICV administration of calcitonin. 4) Depletion of brain serotonin with the neurotoxin 5, 7-dihydroxytryptamine did not influence calcitonin-induced gestric acid suppression. In this study it was demonstrated that centrally- administered calcitonin suppresses baclofen-induced gastric acid secretion. Also. it is suggested that the serotonergic system is not involved in calcitonin-induced gastric acid suppression.

세포내 기록법으로써 검출한 망막 신경원의 동적 특성

이성종,정창섭,배선호 한국의학물리학회 1998 의학물리 Vol.9 No.2

세포내 기록법으로써 메기 망막의 제3열신경원에 대한 동적 특성을 관찰하였다. 메기(channel catfish; Ictalurus punctatus)로부터 안구를 적출한 다음 각막, 홍채, 수정체, 초자체 둥을 차례로 제거함으로써 반구형의 eyecup 표본을 만들었다. 이 표본에 Ringer 용액 또는 실험용액을 관류시키면서 빛자극을 가함에 따라 신경원에서 발생하는 전압변동을 유리 미세전극을 통하여 검출하고 amplifier로써 증폭한 후 penwriter를 이용하여 기록하였다. 빛자극원으로는 컴퓨터 모니터를 이용하였으며, 막대형 자극의 이동속도 및 두께를 조절함으로써 대상 신경원의 위치를 포착하고 방향선택성을 조사하였다. GABA$_{B}$ 수용체 작용제인 baclofen에 의해 제3열신경원의 일종인 ON-지속성 신경원에서 암막전압은 과분극되며 지속성 성분은 억제된 반면 일과성 성분은 증대되었으며, 또한 ON-OFF 일과성 신경원은 특정 방향의 자극에 대한 빛반응이 선택적으로 억제되는 방향선택성을 나타내었다. The dynamic properties of the 3rd-order neuron of the retina was investigated by using conventional intracellular recording techniques. Experiments were performed in the superfused retina-eyecup preparation of the channel catfish, Ictalurus punctatus. The cornea, iris, lens, and vitreous were removed by absorption with Kimwipe tissue under the dissection microscope thereby exposing the retina in a hemi -eyecup. The electrical signal was amplified by electrometer, viewed on oscilloscope. Regular signals from the cells were recorded on a penwriter and stored by data recorder and computer. Full-field, spot or annular light stimuli were generated on a computer monitor and focused onto the retina. Baclofen hyperpolarized the dark membrane potential, suppressed sustained component and enhanced transient component of the ON-sustained cell with a large transient component, but did not affect the surround antagonism of the cell. Baclofen selectively suppressed responses evoked by moving bar light stimuli on the ON-OFF transient cell. The results suggest that transient cells have directional selectivity in the inner retina. These dynamic properties of amacrine and ganglion cells were modulated by baclofen. Therefore, it is presumed that there is baclofen-induced directional selectivity in ON-OFF transient cells in the catfish retina.

Novel extended <i>in vitro-in vivo</i> correlation model for the development of extended-release formulations for baclofen: From formulation composition to <i>in vivo</i> pharmacokinetics

Kim, Tae Hwan,Bulitta, Jü,rgen B.,Kim, Do-Hyung,Shin, Soyoung,Shin, Beom Soo Elsevier 2019 International journal of pharmaceutics Vol.556 No.-

<P><B>Abstract</B></P> <P> <I>In vitro-in vivo</I> correlation (IVIVC), a predictive mathematical model between the <I>in vitro</I> dissolution and the <I>in vivo</I> pharmacokinetics has been utilized for the development of new extended release (ER) formulations. The aim of the present study was to extend the IVIVC approach, which correlates among the formulation composition, the <I>in vitro</I> dissolution, and the plasma drug concentration, to predict plasma drug concentrations from a given composition of the formulation, and vice versa, using baclofen as a model drug. Baclofen ER tablets with different dissolution rates were prepared by varying the composition of hydroxypropyl methylcellulose (HPMC). First, the HPMC compositions and the corresponding <I>in vitro</I> dissolutions parameters were correlated, and then the <I>in vitro</I> dissolution parameters were correlated with the <I>in vivo</I> dissolution parameters extracted from the pharmacokinetic profiles of the baclofen ER formulations <I>via</I> population pharmacokinetic modeling. The final extended IVIVC model linked the composition of the formulation, the <I>in vitro</I> dissolution, and the <I>in vivo</I> plasma concentration profile and was successfully applied for the prediction of <I>in vivo</I> pharmacokinetics from the amount of HPMC in baclofen ER formulations. The present approach holds great promise for designing optimal compositions of ER formulations to present desired plasma concentration profile.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

흰쥐의 척수에서 Cyclic Nucleotides 및 Glipizide가 Baclofen의 심혈관반응에 미치는 영향

고현철,하지희,신인철,Koh, Hyun-Chul,Ha, Ji-Hee,Shin, In-Chul 대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.6

The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B($GABA_B$) receptor on a central regulation of blood pressure(BP) and heart rate(HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula(33-gauge stainless steel) through the guide cannula(PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an $GABA_B$ receptor agonist, baclofen(30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP(50 nmol), a cAMP analog, or glipizide(50 nmol), a ATP-sensitive $K^+$ channel blocker, attenuated the depressor and bradycardic effects of baclofen(100 nmol), but not with 8-bromo-cGMP(50 nmol), a cGMP analog. These results suggest that the $GABA_B$ receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of $K^+$ channel.