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An 8-month-old girl of hypomelanosis of Ito associated with hemimegalencephaly had frequent seizures beginning 44 h after birth. The seizures were secondarily generalized or unilateral initially, followed by infantile spasms at about 1.5 months of age. Frequent partial seizures appeared at 4 months of age. [123I]N-Isopropyl-p-iodoamphetamine (IMP) single photon emission computed tomography (SPECT) was performed serially during an interictal period at 1, 3 and 7 months of age. At 1 and 3 months, IMP-SPECT showed a marked increase of IMP uptake in the pathological left hemisphere and electroencephalography (EEG) revealed left-sided dominant hypsarrhythmia. At 7 months of age, a reversal was seen, there being decreased uptake on SPECT in the pathological hemisphere and abundant high amplitude background activity mingled with epileptic discharges on EEG in the non-pathological hemisphere. These serial changes of IMP uptake on SPECT seemed to reflect either changes in epileptic activity or maturational changes in cerebral perfusion in hemimegalencephaly.

Cocaine- and amphetamine-regulated transcript (CART) was originally discovered as a peptide that increased in the rat striatum after injection of a psychostimulant drug, such as cocaine or amphetamine, and is suggested to play potential roles in drug dependence. We tested the genetic association between the CART gene and methamphetamine (METH) dependence and/or psychosis. The subjects were 203 patients with METH dependence and 239 age- and gender-matched healthy controls. Two single nucleotide polymorphisms (SNPs) of the CART gene, −156A>G and IVS1 + 224G>A, were examined . There were no significant differences in genotype and allele distributions of the polymorphisms between patients with METH dependence and/or psychosis and controls. Neither were significant differences in subgroups of clinical phenotypes, for example, age at first consumption of METH, latency to onset of psychotic symptoms after the first consumption of METH, prognosis of psychosis after therapy, complication of spontaneous relapse to a psychotic state, or multisubstance abuse status, observed. The present findings suggest that the CART gene may not play a pivotal role in the development of METH dependence and psychosis, at least in a Japanese population. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) level in urine has been used for judgment in MA consumption. Metabolism and intoxication of MA are correlated with the activity of cytochrome P450 2D6 (CYP2D6). The activity score (AS) is a potential tool for predicting exposure and personalized dose of drugs metabolized by CYP2D6. Prediction of the CYP2D6 activity score might be described as MA intoxication. The objective of this study was to categorize the CYP2D6 activity score using the urinary amphetamine (AM)/MA ratio. Urine samples (n = 23,258) were collected. The levels of MA and AM were determined by a gas chromatography–nitrogen–phosphorus detector. The log AS was calculated by an AM/MA ratio and classified into four groups following the percentile position: lower than the 2.5th, the 2.5th–the 50th, the 50th–97.5th, and greater than the 97.5th percentile, respectively. The AS value for males presented was less than 0.024, 0.024–0.141, 0.141–0.836, and greater than 0.836. Meanwhile, the AS values were revealed to be lower than 0.023, 0.023–0.148, 0.148–0.850, and higher than 0.850 for females. The AS value of CYP2D6 can be applied to describe the toxicity of MA in forensic crime scenes and relapse behavior. [ABSTRACT FROM AUTHOR]

The article focuses on the study on methamphetamine dependence genes that are considered the main cause behind the existence of human methamphetamine dependence. To test, individuals suffering from this disorder were freed from psychiatric, substance abuse or substance dependence diagnoses, and then their data were compared to matched control subjects who were also treated the same. The result reveals that genes identified by clustered nominally positive single-nucleotide polymorphisms (SNPs) from both samples were unlikely to represent chance observations. This leads to the conclusion that there exists polygenic influences on vulnerability to methamphetamine dependence from genes that are highly unlikely to represent chance observations.

1. Amphetamine (AM) and five amphetamine derivatives, N-ethylamphetamine (NEA), N-butylamphetamine (NBA), 4-methoxyamphetamine (M-AM), 4-methoxy-Nethylamphetamine (M-NEA) and 4-methoxy-N-butylamphetamine (M-NBA) were incubated with microsomal preparations from cells expressing human CYP2D6 to determine whether the enzyme was capable of catalyzing the direct ring oxidation of all substrates; the N-dealkylation of NEA, NBA, M-NEA and M-NBA; and the O-demethylation of M-AM, M-NEA and M-NBA. 2. None of the six compounds examined was N-dealkylated to any extent. 3. The only metabolites produced from AM, NEA and NBA were the corresponding ring 4-hydroxylated compounds, and the rates of formation were low. 4. All ring 4-methoxylated substrates were efficiently O-demethylated by CYP2D6 to their corresponding phenols. The size of the N-alkyl group influenced the rates of formation of these phenolamines. In contrast to reported findings with 2- and 3-methoxyamphetamines, none of the 4-methoxyamphetamines was ring-oxidized in the CYP2D6 enzyme system to 2- or 3-hydroxy-4-methoxyamphetamines or to dihydroxyamphetamines. [ABSTRACT FROM AUTHOR]