We are report on three cases of typical clinical characterstics and treatment response in neuroleptic maligant syndrome(NMS), and reviewed the literatures of NMS. NMS was first recognized as a life-threatening complication of dopamine receptor antagonists, and defined as a catatonic-like states associated with fever, obtundation, muscle rigidity, and unstable vital sign in patients taking neuroleptic agents. Concepts of NMS have changed because medications other than classic neuroleptic drugs have been implicated as triggering agents and syndromes identical to NMS have been observed in other conditions. The important neurochemical features are probably functional dopamine deficiency and ensuing hyperactivity of excitatory amino and neurotransmission in the basal ganglia and hypothalamus. Recognition of NMS and early discontinuation of neuroleptics are the most important step in its management. Supportive care includes management of hyperthermia and fluid replacement. Contraversial therapeutic measures include the application of dopamine receptor agonists, excitatory amino acid antagosists, or dantrolene. Psychiatric patients with a history on NMS and psychotic relapse necessitating antipsycotics do not commonly redevelop NMS.
Antipsychotic Agents ; Basal Ganglia ; Dantrolene ; Dopamine ; Dopamine Agonists ; Dopamine Antagonists ; Excitatory Amino Acids ; Fever ; Humans ; Hypothalamus ; Muscle Rigidity ; Neuroleptic Malignant Syndrome* ; Recurrence ; Synaptic Transmission ; Vital Signs

Pharmacotherapy has been constantly chosen by the clinician among the available treatment options for tinnitus. Medications that have been prescribed off-label to treat tinnitus can be grouped into several categories: benzodiazepines, antidepressants, anticonvulsants, N-methyl-D-aspartate (NMDA) receptor antagonists, dopamine receptor modulators, muscle relaxants, and others. In this article, a wide variety of compounds once used in the treatment of tinnitus and evidenced by clinical trials are reviewed with respect to the mechanisms of action and the drug efficacy. Only a few of the various pharmacological interventions investigated have some beneficial effects against tinnitus: clonazepam, acamprosate, neramexan, and sulpiride. Sertraline and pramipexole were effective in subgroups of patients with psychiatric symptoms or presbycusis. However, no agents have been identified to provide a reproducible long-term reduction of tinnitus in excess of placebo effects. In rodent tinnitus models, L-baclofen, memantine, and KCNQ2/3 channel activators have been demonstrated to reduce tinnitus development. Limitation of the use of an effective high dosage during a longer treatment duration due to dose-dependent side effects of the centrally acting drugs may influence the results in clinical studies. More effective and safer innovative agents should be developed based on the further understanding of tinnitus neural mechanisms and valid animal models, and should be supported by improved clinical trial methodology. The management of tinnitus patients through a tailored treatment approach depending on the detailed classification of tinnitus subtypes will also lead to better treatment outcomes.
Anticonvulsants ; Antidepressive Agents ; Benzodiazepines ; Classification ; Clonazepam ; Dopamine Agonists ; Dopamine Antagonists ; Drug Therapy ; Humans ; Memantine ; Models, Animal ; N-Methylaspartate ; Placebo Effect ; Presbycusis ; Rodentia ; Sertraline ; Sulpiride ; Tinnitus*

PURPOSE: In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine D2 receptor polymorphism in schizophrenic patients. METHODS: The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine D2 receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). RESULTS: The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (chi2(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. CONCLUSIONS: The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.
Alleles ; Antipsychotic Agents* ; Dopamine Antagonists ; Dopamine* ; Humans ; Incidence ; Receptors, Dopamine ; Receptors, Dopamine D2* ; Retrospective Studies ; Schizophrenia

Background: Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted. Objective: Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility. Methods: A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures. Results: No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data. Conclusion Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility.
Endometriosis ; Dopamine Agonists ; Infertility ; Angiogenesis Inducing Agents ; Angiogenesis Inhibitors

This article reviews the characteristics and major pharmacological treatment modalities of bipolar depression, which is distinguished from unipolar depression by etiologic differences, symptomatic features, clinical courses, and treatment responses. Bipolar depression is often disabling and very challenging to treat. In acute and prophylactic phases, mood stabilizers such as lithium, divalproex, and lamotrigine are used as first-line treatment, unless the patient is psychotic or markedly dysfunctional. Carbamazepine and oxcarbazepine can be used as a second-line treatment or in a combination regimen. Depressive episodes that do not respond to mood stabilizers, as well as relapsing episodes despite prophylactic therapy, justify treatment with antidepressants. Many clinicians also advocate the early use of antidepressants and antipsychotics when depressive episodes are severe or psychotic. Selective serotonin reuptake inhibitors and bupropion are considered the first choices for use in combination with a mood stabilizer. Bupropion in particular yields stability against manic switches or cycle acceleration. Traditionally, clinicians have used antipsychotics as a combination option when treating patients with bipolar depression who exhibit psychotic features. However, extensive and well controlled recent studies have shown that atypical antipsychotics such as quetiapine, olanzapine, and an olanzapine/fluoxetine combination can yield therapeutic efficacy and good tolerability for treating bipolar depression with or without psychotic features. In particular, a randomized controlled trial (RCT) using quetiapine monotherapy to treat patients with bipolar depression yielded significantly reduced depressive symptomatology. Other atypical antipsychotics such as amisulpride, aripirazole, risperidone, and ziprasidone have yielded antidepressive efficacy, but no RCT trials have been conducted on patients with bipolar depression. Some preliminary studies have shown that newly developed agents such as dopamine agonist, agomelatine, riluzole, mefepristone, and uridine effectively improve mood symptoms among patients with bipolar depression. More extensive clinical trials are needed.
Acceleration ; Acetamides ; Antidepressive Agents ; Antipsychotic Agents ; Benzodiazepines ; Bipolar Disorder ; Bupropion ; Carbamazepine ; Depressive Disorder ; Dibenzothiazepines ; Dopamine Agonists ; Humans ; Lithium ; Piperazines ; Riluzole ; Risperidone ; Serotonin Uptake Inhibitors ; Sulpiride ; Thiazoles ; Triazines ; Uridine ; Valproic Acid ; Quetiapine Fumarate

This article reviews the characteristics and major pharmacological treatment modalities of bipolar depression, which is distinguished from unipolar depression by etiologic differences, symptomatic features, clinical courses, and treatment responses. Bipolar depression is often disabling and very challenging to treat. In acute and prophylactic phases, mood stabilizers such as lithium, divalproex, and lamotrigine are used as first-line treatment, unless the patient is psychotic or markedly dysfunctional. Carbamazepine and oxcarbazepine can be used as a second-line treatment or in a combination regimen. Depressive episodes that do not respond to mood stabilizers, as well as relapsing episodes despite prophylactic therapy, justify treatment with antidepressants. Many clinicians also advocate the early use of antidepressants and antipsychotics when depressive episodes are severe or psychotic. Selective serotonin reuptake inhibitors and bupropion are considered the first choices for use in combination with a mood stabilizer. Bupropion in particular yields stability against manic switches or cycle acceleration. Traditionally, clinicians have used antipsychotics as a combination option when treating patients with bipolar depression who exhibit psychotic features. However, extensive and well controlled recent studies have shown that atypical antipsychotics such as quetiapine, olanzapine, and an olanzapine/fluoxetine combination can yield therapeutic efficacy and good tolerability for treating bipolar depression with or without psychotic features. In particular, a randomized controlled trial (RCT) using quetiapine monotherapy to treat patients with bipolar depression yielded significantly reduced depressive symptomatology. Other atypical antipsychotics such as amisulpride, aripirazole, risperidone, and ziprasidone have yielded antidepressive efficacy, but no RCT trials have been conducted on patients with bipolar depression. Some preliminary studies have shown that newly developed agents such as dopamine agonist, agomelatine, riluzole, mefepristone, and uridine effectively improve mood symptoms among patients with bipolar depression. More extensive clinical trials are needed.
Acceleration ; Acetamides ; Antidepressive Agents ; Antipsychotic Agents ; Benzodiazepines ; Bipolar Disorder ; Bupropion ; Carbamazepine ; Depressive Disorder ; Dibenzothiazepines ; Dopamine Agonists ; Humans ; Lithium ; Piperazines ; Riluzole ; Risperidone ; Serotonin Uptake Inhibitors ; Sulpiride ; Thiazoles ; Triazines ; Uridine ; Valproic Acid ; Quetiapine Fumarate

Antipsychotics are the drug of choice for patients with schizophrenia, but they can induce hyperprolactinemia and growth of pituitary adenomas by blocking dopamine 2 receptors in the pituitary gland. In contrast, the medical treatment for a prolactinoma is a dopamine agonist. Therefore, managing a patient concurrently diagnosed with a prolactinoma and psychosis is challenging. We describe a patient with schizophrenia who was diagnosed with a prolactinoma. We changed his neuroleptic to quetiapine and prescribed bromocriptine for the prolactinoma. As a result, the patient was successfully treated with a dopamine agonist and antipsychotic without psychotic exacerbation. Our case suggests that dopamine agonists can be administrated to patients with schizophrenia and a prolactinoma without adversely affecting their psychopathological status.
Antipsychotic Agents ; Bromocriptine ; Dopamine ; Dopamine Agonists ; Humans ; Hyperprolactinemia ; Pituitary Gland ; Pituitary Neoplasms ; Prolactinoma ; Psychotic Disorders ; Schizophrenia ; Quetiapine Fumarate

Amenorrhea is one of the well-known side effects of antipsychotics in women. It is associated with hyperprolactinemia induced by dopamine blocking effect of antipsychotics. Administration of bromocriptine which belongs to dopamine agonist may reverse amenorrhea and hyperprolactinemia. However dopamine agonist has been reserved in the treatment of antipsychotics-induced amenorrhea because of concern about exacerbation of psychotic symptoms. This case series study was designed to determine whether bromocriptine can be used safely in schizophrenic patients with amenorrhea. We administered bromocriptine to 5 stable schizophrenic outpatients who experienced amenorrhea over 6 months. Bromocrptine dosage was titrated upward from 2.5 mg/day to 7.5 mg/day until menstrual recovery. Patients' menstrual state and side effects of bromocriptine was monitored prospectively for 22 weeks, and clinical symptom were assessed using brief psychiatric rating scale (BPRS) and clinical global impression scale-severity (CGI-S). These were assessed biweekly until 12th week and then every 4weeks thereafter. All five patients resumed menstruation without deterioration of clinical symptoms measured by BPRS and CGI-S. No serious side effect of bromocriptine was reported. Patients with lower baseline prolactin level showed faster recovery and needed lower dose of bromocriptine. These findings suggest bromocriptine may be used safely in the treatment of antipsychotics-induced amenorrhea.
Amenorrhea* ; Antipsychotic Agents ; Brief Psychiatric Rating Scale ; Bromocriptine* ; Dopamine ; Dopamine Agonists ; Female ; Humans ; Hyperprolactinemia ; Menstruation ; Outpatients ; Prolactin ; Prospective Studies

Avariety of symptoms can occur following traumatic brain injury(TBI) or other types of acquired brain injury. These symptoms can include problems with short-term memory, attention, planning, problem solving, impulsivity, disinhibition, poor motivation, and other behavioral and cognitive deficit. These symptoms may respond to certain drugs, such as dopaminergic agents. Amantadine may protect patients from secondary neuronal damage after brain injury as a effects of NMDA receptor antagonists and may improve functioning of brain-injured patients as a dopaminergic agonist. Clinically, based on current evidence, amantadine may provide a potentially effective, safe, and inexpensive option for treating the cognitive, mood and behavioral disorders of individuals with brain injury. The rationales for using amantadine are discussed, and pertinent literatures are reviewed.
Amantadine* ; Brain ; Brain Injuries* ; Dopamine Agents ; Dopamine Agonists ; Humans ; Impulsive Behavior ; Memory, Short-Term ; Motivation ; N-Methylaspartate ; Neurons ; Problem Solving

Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D(1) and D(2) receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals were tested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animals were then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohistochemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired (higher activity scores) when compared with the control group. Pretreatment with pergolide significantly reduced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the 3rd and 7th days after I/R injury. About 95% neurons in hippocampal CA1 area entered apoptosis and only 2%-7% pyramidal neurons stayed alive due to an inhibition of bcl-2 expression and an increase in bax expression. Pretreatment of pergolide attenuated neuronal damage caused by transient ischemia. Infusion of pergolide could induce the expression of bcl-2 and reduce the expression of bax. Pretreatment with SKF38393, SCH23390 and spiperone had no effects on these changes in this transient I/R injury model. All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis through upregulating the expression of bcl-2 protein and reducing the expression of bax protein.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine ; pharmacology ; Animals ; Apoptosis ; Brain ; physiopathology ; Brain Ischemia ; physiopathology ; Dopamine Agonists ; pharmacology ; Dopamine Antagonists ; pharmacology ; Gerbillinae ; Hippocampus ; physiopathology ; Ischemic Attack, Transient ; physiopathology ; Male ; Neurons ; physiology ; Neuroprotective Agents ; pharmacology ; Pergolide ; pharmacology ; Prosencephalon ; physiopathology ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; biosynthesis ; genetics ; Receptors, Dopamine D1 ; Receptors, Dopamine D2 ; Reperfusion Injury ; physiopathology ; bcl-2-Associated X Protein