Volume 6, Issue 4, December 2004
Sándor Kerpel-Fronius,Miklós Lóránt
Aripiprazole act as a partial agonist on the D2 receptors in contrast to the other antipsychotic agents which exert a pure antagonist action. In the autoreceptors with large receptor reserve aripiprazole shows primarily agonistic action, while postsynaptically its antagonistic action becomes predominant. In addition aripiprazole is an antagonist at the 5-HT2A, receptor and a partial agonist on the 5-HT1 receptor. On the basis of these receptor actions it is suggested that aripiprazole works as a stabilizer of both the dopaminergic and serotoninergic systems. Probably due to this dual stabilizing effect aripiprazole ameliorates positive and negative as well as anxiety and cognitive symptoms. Especially the very rare extrapyramidal symptoms, prolactine level elevation, QT-interval lengthening and absence of severe body weight increase and metabolic disturbances are noteworthy, which all seriously impair the health condition, the quality of life and the therapy adherence of the patients. Due to the very low affinity of aripiprazole to the H1 and muscarinic receptors aripiprazole practically does not lead to increase of body weight. The significant clinical efficacy coupled with good tolerability assures high level clinical effectiveness for aripiprazole in the broad clinical practice.
KEYWORDS: aripiprazole, antipsychotics, dopamine, schizophrenia
Standpoints regarding the pathomechanism of unipolar major depressive disorder (MDD) and the relevant pharmaco-therapeutical possibilities are discussed in the paper. Generations of the antidepressants from the tri- and teracyclic drugs (TCAs) to the modern, dual-acting antidepressants, including the still popular selective serotonin reuptake inhibitors (SSRIs) are surveyed in more detailed. Pharmacodynamic properties of each antidepressant subgroup with the therapeutical benefits, the occasional side-effects and with some characteristic features of the detailed ingredients in certain cases are emphasized. Some benefits and possible disadvantages regarding the combinations are also discussed briefly. The main aim of this review is to give an objective approach to the psychiatrists in order to choose the best and optimal pharmaco-therapeutical method in their daily practice.
KEYWORDS: unipolar major depressive disorder, TCAs, SSRIs, dual-acting drugs, combinations
Emma Birkás, Krisztina Lakatos, Zsófia Nemoda, Krisztina Ney, Ildikó Tóth, Alexa Novák, Mária Sasvári-Székely, Judit Gervai
Association of the 7-repeat allele of the D4 dopamine receptor (DRD4) exon 3 polymorphism with attention deficit/hyperactivity disorder is well-established, and a link with mother-reported aggressiveness was also found in healthy preschoolers assessed by the quantitative scale of the Child Behavior Checklist. In the present study, we hypothesized that children carrying the 7-repeat allele would show more attention problems and externalizing (aggressive and delinquent) behavior at 6 years of age. Further, we hypothesized a potential mediating role of early temperament in the relationship of DRD4 gene with behavior problems. Mothers filled in the Achenbach Child Behavior Checklist for 88 sixyear-old firstborn children (51 boys, 35 girls) followed from birth. Mother-reported temperament for the same children was assessed by the Rothbart Infant Behavior Questionnaire at 12 months. Genotypes of the DRD4 repeat polymorphism were determined using buccal cells. Significant main effects of gender and DRD4 genotype were observed on 6-year behavioral problems. Boys showed more attention problems and externalizing behavior, and children lacking the 7-repeat variant showed more externalizing and internalizing behavior. These effects remained significant after controlling for 1-year temperament. Our results did not confirm the negative effect of the 7-repeat allele on attention problems and externalizing behavior measured on quantitative scales. On the contrary, we found elevated problem scores in the absence of the 7-repeat allele. Further research including environmental risk factors is needed to clarify the role of the DRD4 gene in the development of externalizing behavior.
KEYWORDS:dopamine, genetic risk factors, association study, behavior problems
Zoltán Rihmer, Zsuzsa Kántor, Annamária Rihmer, Krisztina Seregi
Since suicide is a very complex, multicausal human behaviour, its prevention should also be complex. The prediction of suicide is very difficult at the level of the general population, but it is much easier among patients with certain mental disorders, because most persons who kill themselves have diagnosable and treatable psychiatric disorders. This article reviews the most important biological and non-biological suicide prevention strategies.
KEYWORDS: suicide, psychiatric disorders, prevention strategies
A brief summary of the current treatment of Alzheimer disease (AD) (cholinergic replacement therapy, influence of glutamatergic neurotransmission, treatment based on the -amyloid cascade theory, antioxidants, anti-inflammatory drugs) clearly proves that the applied strategies are practically inefficient. We describe therefore the rationale and design of a reasonable clinical trial to test the validity of Knoll’s concept that the administration of a synthetic mesencephalic enhancer substance prior to the precipitation of the symptoms is our only chance to significantly reduce the prevalence of the two main neurodegenerative disorders AD and Parkinson’s disease (PD). Considering that in the population over 65 there are substantial sex (68% female, 32% male) and geographical (highest rate: 10% in USA) differences in the incidence of AD, we propose to perform the clinical trial in 75-85 year old females in the USA. Individuals without (Group 1) and with (Group 2) predisposition to AD should be selected. One third in each group should be treated daily with placebo, (-)-deprenyl (1 mg) and (-)-BPAP (1 mg), respectively. Series of studies proved already the protective effect of the synthetic mesencephalic enhancer substances against age-related neurodegenerative changes in the brain. We may therefore expect a significant difference in the placebo versus drug treated groups in the number of individuals who will precipitate with the passing of time the symptoms of AD or PD. The introduction of a safe and efficient prophylactic therapy that significantly decreases the prevalence of AD is a necessity which cannot be further postponed.
KEYWORDS: Alzheimer´s disease, -amyloid, (-)-deprenyl, (-)-BPAP, enhancer mechanism
Péter Gaszner, Ildikó Miklya
There is still a great need for the development of antidepressants with a new pharmacological spectrum. The finding that phenylethylamine and tryptamine are endogenous enhancers of the impulse propagation mediated release of catecholamines and serotonin in the brain, and the development of synthetic mesencephalic enhancer substances opened the possibility to stimulate catecholaminergic and serotonergic neurons in the mesencephalon via a previously unknown mechanism. (-)-Deprenyl, a prototype of the phenylethylamine-derived synthetic enhancer substances, stimulates the catecholaminergic neurons in the brain but is almost ineffective on the serotonergic neurons. R-(-)-1-(benzofuran-2- yl)-2-propylaminopentane, (-)-BPAP, the recently developed tryptamine-derived selective synthetic mesencephalic enhancer substance, a hundred times more potent compound than (-)-deprenyl, acts also on the serotonergic neurons. The evaluation of the peculiar pharmacological profile of the synthetic mesencephalic enhancer substance, especially the high potency and the unusual safeness and the tolerability of (-)-BPAP cherish the hope that this compound may in the future significantly improve the effectiveness of drug therapy in major depression and its combination with uptake inhibitors may substantially diminish the number of therapy resistant cases.
KEYWORDS: antidepressants, mesencephalic enhancer regulation, endogenous mesencephalic enhancer substances, -phenylethylamine (PEA), tryptamine, synthetic mesencephalic enhancer substances, (-)-deprenyl, (-)-BPAP
Treatment of survivors of political terror is an emerging and difficult field. Reports on posttraumatic stress disorder (PTSD) in political prisoners within the former Eastern Block countries is low and mostly restricted to German sources. During the totalitarian period administrative and clinical decisions often had to take into account political realities not found in other treatment environments. That practice might have lead to biased professional training, lack of experience extending into the post-communist era and leading to current underpresentation of PTSD. The authors present a case report of a Hungarian political prisoner with long history of PTSD who had a “carry over” diagnosis of paranoid schizophrenia even 15 years after the collapse of the communist regime. After decades of continuous administration of antipsychotic and antidepressive medications, either alone or in combination, Zeldox monotherapy has proven to be the most effective treatment for this patient.
KEYWORDS: dissociation, PTSD, schizophrenia, ziprasidone