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/AIMS: Prokinetics are commonly used for the treatment of functional dyspesia, but their methods of action are different. First, we compared the efficacy and safety of the dopamine receptor antagonists, which were domperidone maleate and levosulpiride, in a 2 week treatment in functional dyspepsia, then investigated the efficacy and safety of cisapride tartrate in a 2 week treatment in those who were resistant to domperidone maleate or levosulpiride. METHODS: One hundred Forty-nine patients, who were diagnosed with functional dyspepsia, were selected. The subjects were randomly divided into two groups, domperidone maleate (75) and levosupiride (74). Daily they took 30mg of domperidone maleate (DOM) or 75mg of levosulpiride (LEV) for 2 weeks. Then the subjects who didn't respond to these treatments took 30mg of cisapride tartrate for the following 2 weeks. RESULTS: At week 0, the total symptom scores of the DOM group and LEV group were 8.01+/-2.57 and 8.14+/-2.65 respectively, which were not statistically different. At week 2, the total symptom scores of the DOM and LEV groups were significantly reduced to 4.28+/-3.30 and 4.85+/-3.53(p=0.0001). The efficacy rates of the DOM and LEV groups at week 2 were 50.8% vs. 44.1%. The rate of adverse events in the LEV groups was much higher than in the DOM group(17.7% vs. 8.0%). In addition the rate of change from normal to abnomal in prolactin level was markedly higher in the LEV than that of the DOM group(80.0% vs. 8.3%). After 2 weeks of treatment with cisapride tartrate, the total symptom score was significantly reduced to 3.77+/-2.49(p=0.0001), and the efficacy rate was 75.0%. The satisfaction of the resistant subjects in efficacy of cisapride compared with the previous treatment was 73.3%. The rate of adverse events of cisapride tartrate was 5.0%. CONCLUSIONS: Considering efficacy and safety of domperidone maleate and levosulpiride, domperidone maleate was the safer drug for the treatment of functional dyspepsia, and cisapride tartrate can be a useful drug in those patients who are resistant to dopamine antagonists like domperidone maleate and levosulpiride.
2,5-Dimethoxy-4-Methylamphetamine ; Cisapride* ; Domperidone ; Dopamine Antagonists* ; Dopamine* ; Dyspepsia* ; Gastroesophageal Reflux ; Humans ; Prolactin

Parkinson's disease is the second most common neurodegenerative disease in the world. Beta-arrestin-2 has been reported to be an important protein involved in D(2) dopamine receptor desensitization, which is essential to Parkinson's disease. Moreover, the potential value of pharmacological inactivation of G protein-coupled receptor kinase or arrestin in the treatment of patients with Parkinson's disease has recently been shown. We studied the interaction between D(2) dopamine receptor and beta-arrestin-2 and the pharmacological regulation of chemical compounds on such interaction using capillary zone electrophoresis. The results from screening more than 40 compounds revealed three compounds that remarkably inhibit the beta-arrestin-2/D(2) dopamine receptor interaction among them. These compounds are promising therapies for Parkinson's disease, and the method used in this study has great potential for application in large-scale drug screening and evaluation.
Arrestins ; antagonists & inhibitors ; metabolism ; Dopamine ; metabolism ; Dopamine Antagonists ; therapeutic use ; Dopamine D2 Receptor Antagonists ; Drug Evaluation, Preclinical ; Electrophoresis, Capillary ; Humans ; Parkinson Disease ; drug therapy ; metabolism ; pathology ; Receptors, Dopamine D2 ; metabolism ; Signal Transduction ; beta-Arrestin 2 ; beta-Arrestins

Acamprosate reduces the craving for alcohol by decreasing glutamate activity and increasing gamma-aminobutyric acid (GABA) action in patients with alcohol dependence. Acamprosate has tolerable side effects that include diarrhea, headache, dizziness and pruritus. In this study, we report acamprosate-induced extrapyramidal symptoms in an elderly patient with no history of neurologic disease. Severe extrapyramidal symptoms developed two days after the administration of acamprosate and improved over one week after the acamprosate was stopped. Extrapyramidal symptoms are commonly associated with dopamine receptor antagonists. However, there have been several reports of extrapyramidal symptoms occurring with drugs targeting other systems, including GABA, glutamate and serotonin. Acamprosate may decrease dopamine levels in the ventral tegmental area mediated by glutamatergic action and thus cause extrapyramidal symptoms. We suggest that acamprosate carries the risk of causing extrapyramidal symptoms.
Aged* ; Alcoholism* ; Diarrhea ; Dizziness ; Dopamine ; Dopamine Antagonists ; gamma-Aminobutyric Acid ; Glutamic Acid ; Headache ; Humans ; Pruritus ; Serotonin ; Ventral Tegmental Area

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

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D₃ receptor (D₃R) have effects on addiction in different animal models. We have previously reported that YQA14, a D₃R antagonist, exhibits very high affinity and selectivity for D₃Rs over D₂Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D₃R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats ; Mice ; Animals ; Analgesics, Opioid ; Dopamine ; Heroin/pharmacology* ; Dopamine Antagonists/pharmacology* ; Receptors, Dopamine D3/metabolism* ; Morphine/pharmacology* ; Behavior, Addictive/drug therapy* ; Self Administration

Exclusively dopamine producing retroperitoneal paragangliomas are extremely rare. We have experienced the first Korean case managed successfully based on the proper evaluation. A 26-year-old female patient came to our attention after the accidental detection of an adrenal mass. She had no symptoms and denied any family history. Laboratory evaluations were normal but serum dopamine (425 ng/L) and 24-hour urine dopamine levels (1,565.3 microg/day) were elevated. She underwent laparoscopic right adrenalectomy. Histopathological diagnosis was a paraganglioma. After operation, dopamine levels in serum and 24-hour urine dropped to 0.09 ng/L and 388.4 microg/day. Dopamine producing paraganglioma elicit no clinical symptoms. Only the dopamine level is elevated in serum and 24-hour urine samples. Surgical resection without using preoperative alpha blockage is the treatment of choice. The prognosis for patients with this tumor tends to be poor because the diagnosis is usually delayed due to lack of symptoms.
Adrenal Glands ; Adrenalectomy ; Adrenergic alpha-Antagonists ; Adult ; Dopamine ; Female ; Humans ; Korea ; Paraganglioma ; Pheochromocytoma ; Porphyrins ; Prognosis

OBJECTIVE : We investigated the relationship between the severity of the disease and the abnormality of some ocular movements in parkinson's disease. BACKGROUND: Disorders of eye movements have been described in diseases of the basal ganglia for over a century and ocular motor deficits of the saccadic and pursuit system have been reported in parkinsonian patients. METHOD : We studied the electro-oculography of the eye tracking and saccadic movement in 26 patients (11 males, 15 females) with Parkinson's disease. The severity of the disease was divided into two groups by Hoehn & Yahr(H-Y) staging, H-Y stage 1, 2(group A) and H-Y stage 3, 4 (Group B). Some patients antiparkinsonian drugs of L-dopa, dopamine agonist and anticholinergics. RESULT : The velocity of smooth pursuit and the velocity and latency of saccade were calculated and compared between two groups. Eye tracking test revealed decreased pursuit velocity leading to catch-up saccades, but normal phase relationship between eye and target movement, while saccadic eye movement had increased latency. These results showed more profound severity in more advanced stages of the disease. CONCLUSION : We suggest that ocular movement be often chosen as a simple but relevant example of general motor function, as well as criteria for staging of Parkinson's disease and basal ganglia play significant role in ocular movement.
Basal Ganglia ; Cholinergic Antagonists ; Dopamine Agonists ; Eye Movements ; Humans ; Levodopa ; Male ; Parkinson Disease* ; Pursuit, Smooth ; Saccades

The aim of this study was to examine the effects of various concentrations of glutamate(10(-8), 10(-6) and 10(-4) M) on the circling movement induced by apomorphine in the unilateral substantia nigra-lesioned rats. Subcutaneous apomorphine(0.1 mg/kg) elicited contralateral circling movement(641.7+/-163.9/hr), Glutamate(10(-6)-10(-4) M) significantly reduced the numbers of apomorphine-induced circling movement. This reducing effect of glutamate was antagonized and/or reversed by 10(-7) M GABA antagonist bicuculline. These results suggest that glutamate reduces circling movement induced by apomorphine and this reducing effect of glutamate may be mediated by increased GABA concentration in striatum and substantia nigra.
Animals ; Apomorphine ; Bicuculline ; Dopamine ; GABA Antagonists ; gamma-Aminobutyric Acid ; Glutamic Acid* ; Rats* ; Substantia Nigra

Schizophrenia (SCZ) is a polygenic, multi-factorial disorder and a definitive understanding of its pathophysiology has been lacking since it was first described more than a century ago. The predominant pharmacological approach used to treat SCZ is the use of dopamine receptor antagonists. The fact that many patients remain symptomatic, despite complying with medication regimens, emphasises the need for a more encompassing explanation for both the causes and treatment of SCZ. Recent neuroanatomical, neurobiological, environmental and genetic studies have revived the idea that inflammatory pathways are involved in the pathogenesis of SCZ. These new insights have emerged from multiple lines of evidence, including the levels of inflammatory proteins in the central nervous system of patients with SCZ and animal models. This review focuses on aberrant inflammatory mechanisms present both before and during the onset of the psychotic symptoms that characterise SCZ and discusses recent research into adjunctive immune system modulating therapies for its more effective treatment.
Central Nervous System ; Dopamine Antagonists ; Humans ; Immune System ; Inflammation ; Models, Animal ; Schizophrenia*