Pharmacologic Treatment of Schizophrenia Beyond Dopamine Receptor Blockade-Has Its Time Come Yet?

This Viewpoint describes the need for novel mechanism of action agents for schizophrenia to extend therapeutic options and improve outcomes.

Perfil dopaminérgico del compuesto 2-aminoindano N-aralquil sustituido / Profile dopaminergic of the compound 2-aminoindane substituted N-araquil

El sistema dopaminergico central está implicado en las diversas etiologías que involucran a patologías neuropsiquiátricas, tales como la enfermedad de Parkinson, la depresión y la esquizofrenia. Son numerosas las drogas dopaminérgicas utilizadas en el tratamiento de esas dolencias, sin embargo estas terapias causan serios efectos adversos. En este contexto, la génesis de nuevos y más eficientes agentes dopaminergicos, representa un vasto campo de investigación. En el presente trabajo se sintetizó el compuesto 3, concebido como un ligando dopaminérgico, y se evaluó el perfil de su acción dopaminérgica mediante administración central del compuesto y la determinanción de parámetros conductuales como el comportameinto estereotipado (roer) y la medición de la respuesta renal en ratas. Los resultados de la evaluación farmacológica muestran que el compuesto 3 bloquea significativamente la estereotipia inducida por apomorfina, e inhibe la diuresis y natriuresis inducida por la administración central de dopamina. Estos hallazgos sugieren que el compuesto 3 se comporta como un antagonista dopaminérgico, frente a la respuesta tanto conductuales como renales

Modelo de hipofuncao adenossinergica para esquizofrenia: interacao entre os sistemas purinergico, glutamatergico e dopaminergico / Model of adenosinergic hypofunction for schizophrenia: interactions between purinergic, glutamatergic and dopaminergic systems

Os modelos fisiopatologicos da esquizofrenia classicamente tem abordado diversos neurotransmissores, como a dopamina, a serotonina e o glutamato. Neste trabalho, propomos que alteracoes envolvendo o sistema purinergico...

[Effect of prokinetic drugs inhibiting dopaminergic system on gallbladder motility in subjects with duodenal ulcer]. / Wplyw leków prokinetycznych hamujacych uklad dopaminergiczny na czynnosc ruchowa pecherzyka zólciowego u osób z choroba wrzodowa dwunastnicy.

The purpose of this study was to determine the effect prokinetic drugs inhibiting dopaminergic receptors on gallbladder volume in normal conditions. The study comprised 90 males, aged 20-26 years with duodenal ulcer disease in remission alloted into 3 groups, 30 subject each. The gallbladder volume was determined in group I after placebo or 10 and 20 mg or metoclopramide administration; in group II: placebo or 10 and 20 mg of domperidone and in group III after placebo or 50 and 100 mg of sulphiride administration. Gallbladder motility was assessed ultrasonographically from 15 minutes to 2 hours since placebo or drug administration. The effect of the studied prokinetic drugs in fasting on gallbladder motility was differentiated after metoclopramide no significant changes in gallbladder volume were observed; after domperidone in the dose of 20 mg a slight decrease of gallbladder volume was found, whereas after sulphiryde statistically significant decrease was detected.

Dopamine: pharmacologic and therapeutic aspects.

Dopamine is a biogenic amine synthesized in the hypothalamus, in the arcuate nucleus, the caudad, and various areas of the central and peripheral nervous system. It has been widely established that dopamine and its agonists play an important role in cardiovascular, renal, hormonal, and central nervous system regulation through stimulation of alpha and beta adrenergic and dopaminergic receptors. There are several agonists of dopamine-2 (DA 2 ) dopaminergic receptors, such as bromocriptine, pergolide, lisuride, quinpirole, and carmoxirole, which inhibit norepinephrine release and produce a decrease in arterial blood pressure; in some cases, bromocriptine and pergolide also reduce heart rate. From a therapeutic point of view, the above-mentioned agonists are used for treating Parkinson's disease, acting over DA 2 dopaminergic receptors of the nigrostriatal system. Bromocriptine and the other dopaminergic agonists mentioned act over DA 2 receptors of the tuberoinfundibular system, inhibiting prolactin release and decreasing hyperprolactinemia and tumor size. Among DA 1 receptor agonists, we can mention fenoldopam, piribedil, ibopamine, SKF 3893, and apomorphine (nonspecific). Activation of these receptors decreases peripheral resistance, inducing lowering of arterial blood pressure and increases in heart rate, sympathetic tone, and activity of the renin aldosterone system. Among DA 2 receptor antagonists, we can mention metoclopramide, domperidone, sulpiride, and haloperidol. From a therapeutic point of view, metoclopramide and domperidone are used in gastric motility disorders, and haloperidol is used in psychotic alterations. Antagonists of DA 1 receptors are SCH23390 and clozapine. Clozapine is used for treating schizophrenia.

Dopamine and dopamine receptor agonists in cardiovascular therapy.

Dopamine (DA)--previously regarded simply as the precursor of norepinephrine--is now known to have its own unique effects on cardiovascular regulation which are mediated, in part, by activating specific DA receptors. DA has long been used in the treatment of shock and heart failure. In recent years it has been used at low infusion rates for its renal effects, in combination with other more specific inotropic or pressor agents. Lack of oral bioavailability has limited its use in long-term therapy, however; levodopa and dopa conjugates which are orally absorbed and metabolized to the active form are under investigation. The novel DA1 receptor agonist fenoldopam is claiming a role in the management of hypertension, heart failure, and the preservation of renal function. DA2 receptor agonists are also being evaluated as potential antihypertensive agents.

Enfermedad de Parkinson / Parkinson's disease

Los avances farmacológicos respecto al Síndrome de Parkinson no han sido significativos en los últimos años, sin embargo, si han existido cambios notables en la fisiopatología; sobre todo en lo que respecta a los posibles neurotrasmisores, neuromoduladores o neuropéptidos que participan en esta patología. Evidencias recientes demuestran la presencia de diferentes neuropéptidos en las regiones cerebrales relacionadas con el Parkinson (angiotensina, substancia P, colecistokinina). El presente artículo hace notar que en el Síndrome de Parkinson no sólo hay alteraciones de dopamina y acetilcolina sino que también se modifica la neurofisiología de otros neurotrasmisores y neuropéptidos. Se describe así mismo en forma somera ciertos factores de importancia que hay que considerar en la farmacoterapia que se utiliza en esta patología