(Preliminary text, to be edited) Relatively low daily dose, low hepatic extraction and high brain receptor affinity may point to insignificant hepatic exposure. No capacity for significant pharmacokinetic Cyp-inducing or Cyp-inhibiting effects in clinical use. No porphyrogenic effects connected with the pharmacodynamic inhibitory/exitatory effects on brain receptor functions. No porphyrogenic effects connected with hyperglycemia or other components of the metabolic syndrome potentially accompanying the common weight gain under aripriprazol tretament.(Thunell et al 2011; In manuscript). Weight reduction secondary to anorexia may also be a side effect, and motivates attention to the nutrition of the patient.

Dichlorophenyl - piperazinyl butoxy- kinolinon. Two tertiary and one secondary cyckic amine functions

Indications: Schizophrenia (not in children <15y). Bipolar disorder in manic phase. Administration mode, dose Sublingual, peroral or parenteral 10-15 (-30) mg/d. Atypic antipsychotic drug with affinity to brain dopamine and serotonicne recep-tors. The effect may be mediated through a combination of partial dopamine D2 and serotonin 5HT1a receptors agonism, and antagonism at serotonin 5HT2a receptors. There is also moderate affinity to serotonin re-uptake receptors. Confounding side effects. Common: Nausea, vomiting, obstipation, dyspepsia, restlessness, insom-nia, anxiety. Less common: Tachycardia, depres-sion. Unknown frequency: Agitation, suicidal risk. Physiological effects and bye-effects of possible relevance to acute porphyria. Hyperglycemia and diabetes mellitus, as well as weight gain appearing to be slight (Martindale), has been observed as side effects to treatment with aripiprazole. Increased appetite, weight gain with increased plasma levels of triglycerides, LDL-cholesterol and glucose are common in treatment with atypical antipsychotics, and are the cardinal features of the metabolic syndrome. Increased appetite and weight gain with abdominal adiposity connected with the pre-diabetic and pre-atherosclerotic metabolic syndrome, is caracterized by insulin resistance, hyperinsulinemia, hyperglycemia, cortisolemia and increased triglyceride and cholesterol levels. This is also observed in first episode psychoses prior to pharmacotherapy, indicating a mixed origin (PMID 18370698). Excess fatty acid is implicated in the pathogenesis of insulin resistance (PMID 18154189). The origin of the metabolic syndrome may thus be found in drug- or cortisol-induced increase in appetite - augmented food intake - chylomicronemia - augmented triglyceride hydrolysis in preportal fatty tissue via insulin-stimulated tissue lipoprotein lipase - strongly increased fatty acid (FA) traffic through the liver -increased hepatic VLDL formation - fatty liver - impaired hepatic insulin extraction from blood - hyperinsulinemia - insulin resistance - hyperglycemia. The visceral adipose tissue is not only an energy depot but also an endocrine organ which produces a large number of bioactive molecules. In the setting of obesity, overproduction of pro-inflammatory and pro-thrombotic adipokines is associated with insulin resistance (PMID 21196255), and PXR-inhibitory effects through the activation of NF-kB. Fatty acid-activated peroxisome proliferators-activated receptor (PPAR) isotypes may play beneficiary roles in the metabolic syndrome (PMID 20932114), through PPARb/d augmenting hepatic FA oxidation in muscle, through fatty tissue PPARg faciliating uptake of FA, lipid and glucose as well as stimulating glucose oxidation, and through PPARa participating in FA beta and omega oxidation mainly in liver and heart and ameliorate insulin resistance. These effects are taken advantage of in the treatment of diabetes through use of PPAR agonists. In rodents, carbohydrate response element binding protein (ChREBP) activated by feeding or glucose, reduces metabolic syndrome obesity, fatty liver and glucose intolerance by way of inhibition of glycogenolytic genes and activation lipogenic genes converting excess carbohydrate into triglyceride rather than glycogen (PMID20842602). Clusterin is a stress-response protein contributing to the protein cargo of HDL and involved in diverse biological processes including lipid transport and inflammation. Its expression is increased by glucose, and insulin-activated SREBP-1c plays a crucial role in its metabolic regulation (PMID 21549685). The concentration of clusterin in HDL is lower in conditions with low plasma HDL and high plasma triglyceride concentrations, the key lipid characteristics of the metabolic syndrome. HDL clusterin levels are also lower in individuals with higher body mass index and reduced insulin sensitivity (PMID 20847305).

Minimal pre-systemic metabolism by Cyp3A4 and Cyp2D6. In therapeutic use there are no effects recorded on the metabolism of drugs metabolized by Cyps3A4, 2D6, 2C19, 2C9 or 1A2.

There are yet no reports of the use of aripriprazol in acute porphyrias.