Korean Medication Algorithm for Bipolar Disorder 2018 : Depressive Episode / 우울ㆍ조울병

OBJECTIVES: Since the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002, the fourth revision of KMAP-BP was completed in 2018 in order to reflect the recent rapid research and development into bipolar disorder and psychopharmacology.METHODS: According to the methodology of previous versions, KMAP-BP 2018 was revised using a questionnaire consisting of 10 questions. Among eighty-four experts of the review committee, sixty-one completed the survey.RESULTS: The first-line pharmacotherapeutic strategy for acute bipolar depressive episode with moderate, non-psychotic severe and psychotic severe episode was mood stabilizer (MS) combined with atypical antipsychotic (AAP) or AAP with lamotrigine. Switching or adding AAP, lamotrigine, or MS as 2nd strategies and clozapine or augmentation of buspirone, stimulant, or thyroid hormone as 3rd strategies were recommended. Compared to the previous KMAP-BP series, preference of AAP and lamotrigine has increased in the treatment of bipolar depressive episode in KMAP-BP 2018. Among the AAPs, olanzapine, quetiapine, and aripiprazole were preferred.CONCLUSION: Compared with the previous versions, we found that more active pharmacological strategies using AAP and lamotrigine as initial and next treatment strategies, respectively, were preferred, although few drugs were approved for bipolar depression.

Attenuation of methylphenidate-induced sensitization by co-administration of buspirone

Methylphenidate, which inhibit dopamine transporter is effective in the treatment of ADHD [attention deficit hyperactivity disorder], but long term use of this drug is often associated with addiction and dependence. Locomotor sensitization development to psychostimulants like methylphenidate is an important contributor to drug abuse induced by psychostimulants. Different studies have shown that long term administration of drugs of abuse increases the effectiveness of 5-hydroxytryptamine [5-HT][-1A] somatodendritic receptors. Repeated buspirone administration reduces the effectiveness of 5-HT[1A] somatodendritic receptors. This study was designed to determine that buspirone coadministration may reduce methylphenidate-induced sensitization. The motor activity was compared by using familiar and novel environments after long-term administration of methylphenidate, buspirone and their co-administration. Long term oral administration of methylphenidate at a dose of 2.0mg/kg/day enhanced motor activity in home cage i.e activity of familiar environment monitored at alternate day. Locomotor enhancing effects of methylphenidate were augmented on 13[th] day of drug administration suggesting sensitization induced by the drug. The sensitization effects were significant in home cage monitored on alternate day and also in an open field monitored weekly. Buspirone co-administration at a dose of 10mg/kg/day prevented methylphenidate-induced sensitization. It is suggested that the sensitization development to methylphenidate may oppose by buspirone co-administration due to the reduction in the sensitivity of 5-HT[1A] somatodendritic receptors. These findings may help extend future therapeutics in ADHD

Attenuation of methylphenidate-induced tolerance on cognition by buspirone co-administration

Methylphenidate as a psycho stimulant drug has been prescribed in neuropsychiatric disorders to increase cognition and attention therefore is a medication of choice for attention-deficit/hyperactivity disorder however long-term administration of central nervous system stimulant produces tolerance on cognitive behavior. Previously it has been shown that long-term psychostimulant administration increases somatodendritic5HT-[IA] receptors effectiveness. Repeated buspirone administration attenuates 5-HT[IA] soma to dendritic receptors effectiveness. This study was designed to determine that buspirone co-administration may reduce methylphenidate-induced tolerance on cognitive behavior. Cognitive effects were compared by using water maze and passive avoidance test weekly after long-term administration of methylphenidate, buspirone and their co-administration. Methylphenidate at a dose of 2.0mg/kg/day in rats initially improve memory but after long-term treatment produce tolerance on cognitive behavior this effect is more pronounce in case of spatial working memory of water maze test than passive avoidance learning memory. However oral buspirone co-administration at a dose of 10mg/kg/day prevents methylphenidate-induce tolerance on cognition. It is suggested that buspirone may oppose methylphenidate-induced cognitive tolerance by reducing the sensitivity of 5-HT1A soma to dendritic receptors. These findings may help to extend future therapeutics in ADHD

Buspirone along with melatonin attenuates oxidative damage and anxiety-like behavior in a mouse model of immobilization stress / 中国天然药物

AIM@#Stress is recognized to precipitate anxiety and related psychological problems characterized by a wide range of biochemical and behavioral changes. The present study was carried out to investigate the protective effects of melatonin and buspirone, and their combination, against six hours immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice.@*METHOD@#Male Laca mice were pre-treated with melatonin (2.5, 5 mg·kg(-1)), buspirone (5, 10 mg·kg(-1)), and their combination for consecutive five days. On the 6(th) day, animals were immobilized for six hours, and thereafter various behavioral tests were performed followed by biochemical tests.@*RESULTS@#Immobilization stress significantly impaired body weight, locomotor activity, and caused anxiety-like behavior, along with increased oxidative damage. Pretreatment with melatonin and buspirone significantly improved the loss in body weight and locomotor activity, attenuated anxiety-like behavior (in both the mirror chamber and plus maze performance tasks), further restored the levels of brain total proteins, and caused antioxidant-like effects, as evidenced by reduced lipid peroxidation, nitrite concentration, and restoration of reduced glutathione and catalase activity, as compared to control animals. In addition, combination of melatonin (2.5, 5 mg·kg(-1)) with buspirone (5 mg·kg(-1)) significantly potentiated their protective effects, as compared to their effects individually.@*CONCLUSION@#The present study suggests that melatonin potentiates the beneficial effect of buspirone against immobilization stress-induced, anxiety-like behavioral and oxidative damage in mice possibly by involving a serotonergic mechanism.

Aspectos farmacológicos, efeitos anticonvulsivantes e neuroprotetores da buspirona / Pharmacological study of buspirone and its anticonvulsant and neuroprotective effects

A buspirona é o primeiro fármaco da classe das azapironas e a única comercializada no Brasil. O objetivo do presente trabalho foi conduzir uma revisão de literatura sobre os aspectos farmacológicos da buspirona, bem como demonstrar seus efeitos anticonvulsivantes e neuroprotetores no modelo de convulsão induzido por pilocarpina. Para tanto, foi realizada uma revisão da literatura usando as palavras-chaves buspirone, action mechanism, pharmacokinetics, indications, adverse effects, nomenclature e structure, por intermédio do MEDLINE e LILACS, bem como foram inseridos os resultados experimentais encontrados em camundongos pré-tratados com buspirona no modelo de convulsão induzido por pilocarpina. A busca incluiu todos os artigos completos, resumos, estudos de caso, pré-clínicos e clínicos nos idiomas português e inglês compreendidos entre os anos de 1982 e 2010. Com base na revisão, pode se perceber que ainda existem muitas questões sem respostas sobre a farmacologia da buspirona. Somente a descrição do mecanismo de ação é insuficiente para explicar todos os efeitos produzidos pela buspirona. Além disso, em nossos estudos farmacológicos demonstramos que a buspirona apresenta efeitos anticonvulsivantes e neuroprotetores em camundongos no modelo de convulsão induzido por pilocarpina. Existem poucas informações na literatura sobre o mecanismo de ação que explicaria os efeitos adversos da buspirona, bem como suas propriedades anticonvulsivantes e neuroprotetoras. Dessa forma, são necessários mais estudos para fornecer as informações necessárias, bem como para esclarecer as suas propriedades farmacológicas, contribuindo com o conhecimento dos profissionais, a fim de prevenir os efeitos adversos durante o tratamento clínico com a buspirona.

Buspirone was the first drug in the class of azapirones and is the only one marketed in Brazil. The objective of this study was to conduct a literature review on the pharmacology of buspirone, as well as to demonstrate its neuroprotective and anticonvulsant effects in the model of seizures induced by pilocarpine. To this end, we employed the keywords buspirone, action mechanism, pharmacokinetics, indications, adverse effects, nomenclature and structure to perform a search of the literature, through MEDLINE and LILACS, and inserted the experimental results obtained in mice pretreated with buspirone in the model of seizures induced by pilocarpine. The search included all full articles, abstracts, case studies, pre-clinical and clinical studies in Portuguese and English, between the years 1982 and 2010. The review revealed that there are still many unanswered questions about the pharmacology of buspirone. A description of the mechanism of action alone is insufficient to explain all the effects produced by buspirone. Moreover, our pharmacological studies have shown that buspirone has anticonvulsant and neuroprotective effects in a mouse model of seizures induced by pilocarpine. There is little information in the literature about mechanisms that would explain either the adverse effects of buspirone or its anticonvulsant and neuroprotective properties. Thus, further studies are needed to provide the necessary information, as well as to clarify its pharmacological properties, in order to enable professionals to prevent adverse effects during clinical treatment with buspirone.

Efeito antioxidante da buspirona no modelo de epilepsia induzida por pilocarpina / Antioxidant effect of buspirone in epilepsy model induced by pilocarpine

CONTEXTO: Crises epilépticas induzidas por pilocarpina podem produzir alterações histopatológicas em muitas regiões cerebrais como consequência da produção excessiva de radicais livres.OBJETIVO: O objetivo do presente estudo foi avaliar o efeito antioxidante da buspirona no modelo de epilepsia induzida por pilocarpina.MATERIAL E MÉTODOS: Quarenta e oito animais foram divididos em quatro grupos. O primeiro grupo foi tratado com solução salina 0,9% (Controle). O segundo grupo foi tratado com pilocarpina 400 mg/kg (P400). Por sua vez, o terceiro grupo foi tratado com buspirona 5 mg/kg (BUSP) durante 14 dias consecutivos. Já os animais do quarto grupo foram tratados com buspirona durante 14 dias consecutivos, e, 30 minutos após a última administração dela, os camundongos receberam P400 (BUSP + P400).RESULTADOS: Durante o período do tratamento não se observaram sinais de toxicidade e nenhuma morte entre os animais tratados com buspirona. Em nosso estudo o grupo tratado com P400 demonstrou um aumento significativo da produção de nitrito e nos níveis de peroxidação lipídica após as crises epilépticas. Por outro lado, no hipocampo dos animais que receberam o pré-tratamento com buspirona e após 30 minutos receberam P400, foi observada redução significativa nos níveis de peroxidação lipídica (65%) e nitrito (85%), bem como aumento na atividade da enzima superóxido dismutase.CONCLUSÃO: O pré-tratamento com BUSP aumentou a latência para primeira crise epiléptica e diminuiu a taxa de mortalidade e o número de animais que apresentaram crise epiléptica e que progridem para o estado de mal epiléptico. Além disso, apresentou efeitos anticonvulsivantes associados com a redução do estresse oxidativo hipocampal no modelo de epilepsia induzida por pilocarpina.

BACKGROUND: Pilocarpine-induced seizures can cause pathological changes in many brain regions as a result of excessive production of free radicals.OBJECTIVE: The objective of this study was to evaluate the antioxidant effect of buspirone in the epilepsy model induced by pilocarpine.MATERIAL AND METHODS: Forty-eight animals were divided into four groups. The first group was treated with saline 0.9% (control); the second group received pilocarpine 400 mg/kg (P400); the third group was treated with buspirone 5 mg/kg (BUSP) for 14 consecutive days and animals in the fourth group were treated with buspirone for 14 consecutive days, and 30 minutes after the last buspirone administration were administered with P400 (BUSP + P400).RESULTS: No toxicity signs or death were observed in buspirone-treated animals. P400 group showed a significant increase in nitrite production and lipid peroxidation after seizures. Moreover, reduction in both the lipid peroxidation level (65%) and nitrite content (85%) as well as an increase in superoxide dismutase activity was detected following P400 injection in the hippocampus of buspirone-pretreated mice.DISCUSSION: Pretreatment with BUSP increased latency to first seizure, decreased the mortality rate and number of animals that presented seizures and progression to status epilepticus, showing potent anticonvulsant effects associated with reduction of hippocampal oxidative stress.

[Study the effect of buspirone and trazodone on hematological damage induced by long-term exposure to noise in mice]

The study investigated the effect of stress induced by long-term exposure to noise on body immunity through total white blood cell and lymphatic cell count, and on neutrophil-to-lymphatic cell ratio as a physiological marker of noise-induced stress in rats. In addition, the effect of both buspirone and trazodone in alleviating this negative outcome induced by noise was also investigated on 32 rats aged 90-100 days at the beginning of the study period. Results of the study was consistent with previous theories that noise may be considered as a causative agent which influences body's immune system when it reduces both total white blood cell and lymphatic cell count. Results also showed that the ration of neutrophil-to-lymphatic cell was increased as a result of long-term exposure to noise. Furthermore, the study presented a new evidence of antagonizing and therapeutic effect of buspirone and trazodone to stress-induced physiological damage

Effect of pomegranate pretreatment on the oral bioavailability of buspirone in male albino rabbits

Many drug substances and variety of naturally occurring dietary or herbal components are capable of interaction with the CYP enzyme system. The aim of the study was to investigate the effect of pomegranate juice pretreatment on the bioavailability of buspirone in rabbits. White New Zealand rabbits weighing 2.1 +/- 0.13 Kg were selected for study. The bioavailability of buspirone after pre-treatment with pomegranate juice [10 ml Kg-1 for seven days] was compared with an oral solution of 10 mg kg-1 of buspirone in distilled water. Animals were allowed free access to food and water, until night prior to dosing and were fasted for 10 hrs. In the first phase oral solution [10 mg kg-1] was administered through feeding tube followed by rinsing with 10 ml of water. In the second phase, the group was pretreated with pomegranate juice for 7 days and study was conducted after 15 days of washout period. The results showed that there was a significant [p<0.05] difference in the bioavailability of buspirone after pre-treatment with pomegranate juice. This increase in bioavailability might be due to inhibition of CYP3A4. Further studies are required to prove this mechanism in humans

Korean Medication Algorithm Project for Generalized Anxiety Disorder 2009 (II) : Medication Algorithm & Long-Term Medication Treatment Strategy / 신경정신의학

OBJECTIVES: This study was performed to investigate the consensus about medication algorithms, including long-term medication treatment strategies, in the treatment of generalized anxiety disorder (GAD). METHODS: The executive committee of the Korean Medication Algorithm Project for GAD developed questionnaires about the psychopharmacologic treatment strategies for patients with GAD. Fifty-five (65%) of 84 experts of a reviewing committee answered the questionnaires. The consensus of expert opinion was classified into three categories, and the treatments of choice were selected by use of 95% confidence intervals and chi-square-tests. RESULTS: The consensus on the first-line treatment strategy for GAD was as follows. Step 1 is the use of the one of a selective serotonin reuptake inhibitor (SSRI), a serotonin and noradrenaline reuptake inhibitor (SNRI) and buspirone for at least four to six weeks. Step 2 is to switch from a SSRI to a SNRI or buspirone or vice versa. Step 3 is to augment medication with an atypical antipsychotic or add a benzodiazepine or antihistamine. Step 4 is to switch to another combination, which includes a SSRI, a SNRI, mirtazapine or a tricyclic antidepressant Step 6 is to review the diagnosis, and 'benzodiazepines including clonazepam and alprazolam can be combined with another drug even from the initial period'. In terms of long-term medication treatment, the consensus first-line tr-eatment strategy involved the use of venlafaxine XR, escitalopram, fluoxetine, paroxetine CR, sertraline and buspirone. CONCLUSION: This study provided information about the consensus among Korean experts regarding medication algorithms, including long-term medication treatment strategies, in the treatment of GAD.

Dose-dependent response of central dopaminergic systems to buspirone in mice.

Buspirone, a partial agonist of 5-hydroxytryptaminelA autoreceptors, preferentially blocks the presynaptic rather than the postsynaptic D2 dopamine (DA) receptors. Behavioural effects of a wide dose range of buspirone were therefore studied in mice. Buspirone at 0.625 to 5 mg/kg ip induced stereotyped cage climbing behaviour which was antagonized by pretreatment with haloperidol, alpha-methyl-p-tyrosine and small doses of apomorphine. Buspirone at 10, 20 and 40 mg/kg ip induced catalepsy and antagonized oral stereotypies induced by high doses of apomorphine and methamphetamine and apomorphine-induced cage climbing behaviour. The findings indicate that buspirone at 0.625 to 5 mg/kg selectively blocks the presynaptic mesolimbic D2 DA autoreceptors and releases DA which stimulates the postsynaptic mesolimbic D2 and D1 DA receptors and induces cage climbing behaviour. Buspirone, at 10, 20 and 40 mg/kg blocks the postsynaptic striatal and mesolimbic D2 and D1 DA receptors. Pretreatment with 1-tryptophan, dexfenfluramine and fluoxetine antagonized buspirone induced cage climbing behaviour and potentiated buspirone induced catalepsy. Pretreatment with trazodone, mianserin and p-chlorophenylalanine potentiated buspirone induced cage climbing behaviour and antagonized buspirone induced catalepsy. The results indicate that drugs which influence the activity of central serotonergic systems modulate the intensity of buspirone induced cage climbing behaviour and catalepsy.

Effects of buspirone on dopamine dependent behaviours in rats.

Buspirone, a partial agonist of 5-hydroxytryptamine autoreceptors, selectively blocks presynaptic nigrostriatal D2 dopamine (DA) autoreceptors. At doses which antagonised action of apomorphine in biochemical presynaptic nigrostriatal D2 DA autoreceptor test systems buspirone neither induced catalepsy nor antagonised apomorphine-induced turning behaviour in rats indicating that at these doses buspirone does not block postsynaptic striatal D2 and D1 DA receptors. This study determines whether at high doses buspirone blocks postsynaptic striatal D2 and D1 DA receptors and provides behavioural evidence for selective blockade of presynaptic nigrostriatal D2 DA autoreceptors by smaller doses of buspirone. We investigated in rats whether buspirone induces catalepsy and effect of its pretreatment on DA agonist induced oral stereotypies and on cataleptic effect of haloperidol and small doses (0.05, 0.1 mg/kg, ip) of apomorphine. Buspirone at 1.25, 2.5, 5 mg/kg, ip neither induced catalepsy nor antagonised apomorphine stereotypy but did potentiate dexamphetamine stereotypy and antagonised cataleptic effect of haloperidol and small doses of apomorphine. Buspirone at 10, 20, 40 mg/kg, ip induced catalepsy and antagonised apomorphine and dexamphetamine stereotypies. Our results indicate that buspirone at 1.25, 2.5, 5 mg/kg blocks only presynaptic nigrostriatal D2 DA autoreceptors while at 10, 20, 40 mg/kg, it blocks postsynaptic striatal D2 and D1 DA receptors. Furthermore, buspirone at 1.25, 2.5, 5 mg/kg by selectively blocking presynaptic nigrostriatal D2 DA autoreceptors, increases synthesis of DA and makes more DA available for release by dexamphetamine and during haloperidol-induced compensatory 'feedback' increase of nigrostriatal DAergic neuronal activity and thus potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.

Potencialização do tratamento antidepressivo / Antidepressive treatment potentialization

A depressão é um transtorno crônico e recorrente, e está associada com prejuízo funcional, morbidade e mortalidade. Embora a remissão tenha sido identificada como o principal objetivo do tratamento, somente 25 por cento a 35 por cento dos pacientes apresentam remissão completa após seis a oito semanas de tratamento. A remissão incompleta, com a presença de sintomas residuais, está associada a elevadas taxas de recorrência e prejuízo das funções sociais. Desde o início da década de 1980, as estratégias de potencialização vêm sendo cada vez mais utilizadas no tratamento da depressão resistente. As potencializações com lítio e T3 são as mais estudadas, mas existem muitas medicações seguras e bem toleradas (como buspirona, pindolol, metilfenidato, antipsicóticos típicos e atípicos) e também antidepressivos freqüentemente utilizados em estratégias de combinação (como trazodona, mirtazapina e bupropiona), que podem ser úteis para se atingir a remissão completa dos sintomas depressivos. Este artigo revisa a base de dados de algumas estragégias de potencialização e combinação de antidepressivos e discute o racional e a utilidade destes tratamentos.

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos / Treatment-resistant depression: review of pharmacologic antidepressant strategies

OBJETIVO: Fazer uma revisão sobre oito estratégias farmacológicas de potencialização de antidepressivos na DRT. MÉTODOS: Fez-se um levantamento bibliográfico de 1990 até janeiro de 2006, nas bases eletrônicas de busca Medline, LILACS e da Biblioteca Cochrane, utilizando-se os termos de busca treatment, resistant, refractory e depression e os descritores depression, drug resistance e augmentation, incluindo apenas ensaios controlados duplo-cegos. Foi consultada a referência dos artigos para obtenção de ensaios realizados em data anterior a 1990 e artigos originais de valor histórico. RESULTADOS: Foram encontrados 17 estudos duplo-cegos com o lítio, seis com o hormônio tireoidiano, dois com a buspirona, seis com o pindolol, um com a carbamazepina, dois com a lamotrigina e quatro com a olanzapina. Foram favoráveis à potencialização 41,2 por cento dos ensaios com lítio; 60 por cento daqueles com hormônio tireoidiano e antidepressivos tricíclicos e nenhum com hormônio tireoidiano e inibidores seletivos da recaptação da serotonina (ISRS); 50 por cento dos com pindolol; 100 por cento dos ensaios com carbamazepina e 40 por cento daqueles com olanzapina. Nenhum dos estudos com a buspirona foi favorável. No único estudo com lamotrigina não houve eficácia de tratamento na avaliação pelo critério principal, mas superioridade ao placebo em critérios secundários. CONCLUSÃO: Na DRT há evidência de eficácia apenas em relação ao lítio na potencialização de várias classes de antidepressivos e ao hormônio tireoidiano na potencialização de tricíclicos. A olanzapina foi razoavelmente estudada e sua eficácia não foi estabelecida. Os poucos estudos realizados com a buspirona e o pindolol não comprovaram sua eficácia. A carbamazepina foi muito pouco estudada, e a lamotrigina ainda não foi adequadamente avaliada.

OBJECTIVE: The aim of this study is to review eight pharmacologic antidepressant augmentation strategies in TRD. METHODS: Database search on Medline, LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. RESULTS: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60 percent of those with thyroid hormone and tricyclics, 0 percent of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI), 50 percent of those with pindolol, 100 percent of those with carbamazepine and 40 percent of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measures. CONCLUSION: Only lithium and thyroid hormone showed efficacy as antidepressant augmentation strategies for TRD. Olanzapine was reasonably studied and did not prove its efficacy. There were just a few studies on buspirone and pindolol and they were not favorable to them. Carbamazepine was studied very little. Lamotrigine was not adequately evaluated.

Pharmacotherapy of Anxiety Disorders in Older People

Anxiety disorders are common psychiatric illnesses in the elderly. However, anxiety disorders in older people have not drawn much attention from researchers and clinicians alike, compared with late-life depression or dementia. The author searched for articles published from 1986 to 2006 using the key words including "anxiety", "elderly", "aged", and "pharmacological" therapy in the MEDLINE, PsychINFO, and KMbase in order to clarify effective pharmacological therapy in the elderly with anxiety disorders. Well designed studies for pharmacologic intervention in late-life anxiety disorders were rarely found. Nonetheless, studies on young adults demonstrated a number of pharmacological treatment options that can be applied to these patients. Pharmacologic treatments for the elderly include therapies using antideprssants, especially SSRI or SNRI, buspirone, or benzodiazepines. The latter requires special caution in the administration in the elderly because it can lead to adverse events. Therefore, well designed clinical trials are further needed to obtain optimal pharmacological intervention for the elderly with anxiety disorders.

Involvement of central serotonergic systems in dextromethorphan-induced behavioural syndrome in rats.

Dextromethorphan, a noncompetitive blocker of the N-methyl-D-aspartate (NMDA) type of glutamate receptor, at 45, 60 and 75 mg/kg, ip doses induced a behavioural syndrome characterised by reciprocal forepaw treading, lateral head-weaving, hind-limb abduction and flat body posture. Such type of behavioural syndrome is induced by 8-hydroxy-2- (di-n-propylamino) tetralin (8-OH-DPAT) by directly stimulating the central postsynaptic 5-hydroxytryptamine (5-HT, serotonin) receptors of the 5-HT1A type. Pretreatment with buspirone (5, 10 mg/kg, ip) and l-propranolol (10, 20 mg/kg, ip) antagonised the behavioural syndrome induced by 8-OH-DPAT and dextromethorphan. Pretreatment with p-chlorophenylalanine (100 mg/kg/day x 4 days) antagonised the behavioural syndrome induced by dextromethorphan and dexfenfluramine but had no significant effect on 8-OH-DPAT induced behavioural syndrome. This indicates that dextromethorphan induces the behavioural syndrome by releasing 5-HT from serotonergic neurons with resultant activation of the postsynaptic 5-HT1A receptors by the released 5-HT. Pretreatment with fluoxetine (10 mg/kg, ip) significantly potentiated the behavioural syndrome induced by dextromethorphan and 5-hydroxytryptophan but significantly antagonised dexfenfluramine induced behavioural syndrome. This indicates that dextromethorphan releases 5-HT by a mechanism which differs from that of dexfenfluramine. Dextromethorphan may be releasing 5-HT by blocking the NMDA receptors and thereby counteracting the inhibitory influence of l-glutamate on 5-HT release.

Pharmacological Treatment for Nicotine Dependence / 대한정신약물학회지

It was not above two or three decades from the changes began that regarding nicotine dependence as a kind of addictive disorder and a therapeutic target. Despite the short period of history, lots of medications were developed and showing significant clinical outcomes. In this review, we introduce the both of medications available at this time and in the status of developing for nicotine dependence. The clinical efficacies, practical ways of prescription, and common adverse events of the medications currently available are described through the survey of literatures. The novel medications in the process of developing are arranged by the proposed mechanism of action and summarized the phases of clinical trials at present. Among the diverse pharmacological tools now available, nicotine replacement and bupropion could be the first-line recommendation drugs and nortriptyline and clonidine could be the second-line recommendation drugs. Other medications like several antidepressants (e.g., moclobemide), buspirone, and naltrexone may be helpful in some specific population. Most of medications currently available have uncertainties in the aspects of their mechanisms of action except nicotine replacement materials; however, medications in developing have clearer neurobiological basis in their applications. Therefore, we can expect higher treatment outcomes by new products. Additionally, introduction of nicotine vaccines for high-risk group is drawing near. It could be possible for the individualizing for strategies of smoking cessation according to the patients' specific situation in a future.

Diagnosis, and Treatment of Generalized Anxiety Disorder in Primary Practice

Generalized anxiety disorder (GAD) is highly prevalent psychiatric disorder in primary care population and is a source of major morbidity. However, the underawareness and undertreatment of GAD, which is due to insufficient knowledge about the disorder, often hinder the proper management of this chronic condition. Other characteristic features such as chronic course of GAD, frequent comorbidity with other anxiety and depressive disorders, and the controversy regarding the best diagnostic criteria should be fully discussed. First of all, proper and accurate diagnosis is crucial for an appropriate management. Primary care management of GAD and associated comorbidities includes education about the nature of GAD and counseling about treatment alternatives and coping strategies is an important first step. The most effective treatment of GAD is combined psychotherapeutic and pharmacotherapeutic approach. The major psychotherapeutic approaches to GAD are cognitive-behavioral therapy with relaxation techniques. Pharmacological treatment for GAD includes benzodiazepine, buspirone, and antidepressants. In this review, these combined treatment at the view point of primary practitioners was described.

Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats.

Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.