Dopamine system stabilizers

Stahl SM. Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, part 1 Goldilocks actions at dopamine receptors. J Clin Psychiatry 2001 62 841-2. 

The client with paranoid schizophrenia is prescribed aripiprazole (Abilify), a dopamine system stabilizer (DDS). Which statement best describes the scientific rationale for administering this medication ... 

The oxidation of N ADH has been mediated with chemically modified electrodes whose surface contains synthetic electron transfer mediators. The reduced form of the mediator is detected as it is recycled electrochemically. Systems based on quinones 173-175) dopamine chloranil 3-P-napthoyl-Nile Blue phenazine metho-sulphatemeldola blue and similar phenoxazineshave been described. Conducting salt electrodes consisting of the radical salt of 7,7,8,8-trtra-cyanoquinodimethane and the N-methylphenazium ion have been reported to show catalytic effects The main drawback to this approach is the limited stability... 

There is evidence for the contribution of serotonin dysfunction to mania, and in the mechanism of action of mood stabilizers [19], however, specific data on the serotonergic system and mania are fewer and variable. Moreover, altered functioning of other neurotransmitters in mania such as norepinephrine, dopamine, acetylcholine, and GABA, and their interaction with serotonin, are also likely to be involved in the pathogenesis of mood disorders. Differences in these neurotransmitter systems possibly underlie differences in the pathogenesis of depressive and manic episodes. 

If we dehne a mood stabilizer as a medication that is both an effective anti-manic and antidepressant, then lithium arguably remains to this day the prototypical mood stabilizer. Lithium not only reduces the symptoms of acute BPAD, it also prevents the recurrence of additional mood episodes. Despite the fact that lithium has revolutionized the treatment of BPAD and remains nearly 50 years after its introduction as the single best treatment for many patients with BPAD, there is still no consensus as to how it works. Lithium exerts effects on several neurotransmitter systems (e.g., serotonin, dopamine, norepinephrine, acetylcholine), on second messenger systems inside the nerve cell, and on nerve cell gene expression. Yet, precisely how these varied effects produce lithium s therapeutic benefit remains unclear. 

The autoxidation of ascorbate, a cosubstrate of dopamine P-monooxygenase, induces the degradation of most proteins including catalase and dopamine p-monooxygenase, but with the exception of (Cu,Zn)-SOD. Catalase protects dopamine P-monooxy-genase and is therefore generally added in the assay systems . The apparent activation or rather the stabilization of the enzyme (6.5 pg) by small amounts of catalase (3.1 pg) was enhanced by native but not by boiled SOD (100 pg) and also by similar amounts of serumalbumin (100 pg) or of boiled catalase (65 pg)... 

The permissive serotonin hypothesis proposes that serotonin (5-hydroxytryptamine or 5-HT) plays a critical role in modulating brain activity (e.g., stabilization of the catecholamine system and inhibition of dopamine [DA] release), and is low in both mania and depression. L-tryptophan or 5-HT deficiency and changes in the light-dark cycle may result in reduced melatonin secretion from the pineal gland that disrupts the sleep-wake cycle, alters circadian rhythms, and causes seasonal affective changes. ... 

PCP binds to a site within the ion channel of the NMDA receptor that blocks the influx of cations, thereby acting as a non-competitive antagonist. PCP produces a syndrome in normal individuals that closely resembles schizophrenia and exacerbates symptoms in patients with chronic schizophrenia. Ketamine is an anesthetic that has approximately a 10- to 15-fold lower affinity for the NMDA receptor, and it produces the characteristic cognitive deficits of schizophrenia. When ketamine is administered to patients with schizophrenia stabilized with antipsychotic medication, it produces delusions, hallucinations, and thought disorder, consistent with the patient s typical pattern of psychotic relapse. Consistent with this model, chronic PCP administration also increases subcortical dopamine release, particularly in the nucleus accumbens, emphasizing the reciprocal modulation of the glutamate and dopamine neuronal systems in schizophrenia. 

HGG exhibits lower voltammetric background current, comparable electrochemical activity for several redox systems, enhanced S/B ratios, and improved response stability compared with freshly polished (i.e. oxygenated) GC. Relatively rapid electrochemical reaction kinetics were observed for Fe(CN)6 / and Ru(NH3)6 /", while slightly slower kinetics were seen for dopamine and 4-methylcatechol. Very sluggish kinetics were found for Fe" " /" ". For example, apparent heterogeneous electron-transfer... 

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