DISC1

Disrupted in schizophrenia 1 is a protein that in humans is encoded by the DISC1 gene. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, clinical depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research.

Discovery

In 1970, researchers from the University of Edinburgh performing cytogenetic research on a group of juvenile offenders in Scotland found an abnormal translocation in chromosome 1 of one of the boys, who also displayed characteristics of an affective psychological disorder. After this initial observation, the boy's family was studied and it was found that 34 out of 77 family members displayed the same translocation. According to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (or DSM-IV) criteria, sixteen of the 34 individuals identified as having the genetic mutation were diagnosed with psychiatric problems. In contrast, five of the 43 unaffected family members were identified to have psychological indispositions. The psychiatric illnesses observed in the family ranged from schizophrenia and major depression to bipolar disorder and adolescent conduct disorder (which the original research subject had). After studying this large Scottish family for four generations, in 2000, this gene was given the name "DISC1". The name was derived from the basis of the molecular nature of the mutation: the translocation directly disrupts the gene.

AKB48

AKB48 (pronounced A.K.B. Forty-eight) is a Japanese idol girl group named after the Akihabara (Akiba for short) area in Tokyo, where the group's theater is located, and its original roster of 48 members. As of December 2015, the group has expanded to include more than 130 members aged from their early teens to their mid-20s. AKB48's producer, Yasushi Akimoto, wanted to form a girl group with its own theater (unlike pop groups performing occasional concerts and seen on television) and performing daily so fans could always see them live. This "idols you can meet" concept includes teams which can rotate performances and perform simultaneously at several events and "handshake" events, where fans can meet group members. Akimoto has expanded the AKB48 concept to several sister groups in Japan, China and Indonesia.

The group is one of the highest-earning musical performers in Japan, with 2013 sales of over $128 million, and has been characterized as a social phenomenon.As of December 2015 the group has sold over 41 million records, including over 36 million singles and over 5 millon albums. AKB48 is the highest selling musical act in Japan in terms of singles sold and the highest by a girl group. AKB48's twenty-nine latest singles have topped the Oricon Weekly Singles Chart, with a record twenty-three singles selling over a million copies; their highest selling single, "Sayonara Crawl", sold over 1.95 million in 2013. In 2010 "Beginner" and "Heavy Rotation" placed first and second, respectively, on the list of Japan's best-selling singles for the year. In all consecutive years since then, AKB48's singles have occupied the top four or five spots of the Oricon Yearly Singles Chart.

APINACA

AKB48 (APINACA, N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide) is a drug that acts as a reasonably potent agonist for the cannabinoid receptors, with a K_i of 304.5nM and a EC₅₀ of 585nM at CB₁. It had never previously been reported in the scientific or patent literature, and was first identified by laboratories in Japan in March 2012 as an ingredient in synthetic cannabis smoking blends, along with a related compound APICA. Structurally it closely resembles cannabinoid compounds from patent WO 2003/035005 but with a simple pentyl chain on the indazole 1-position, and AKB48 falls within the claims of this patent despite not being disclosed as an example.

Legality

APINACA was made illegal in Japan in 2012, and was banned as a temporary class drug in New Zealand from 13 July 2012.

APINACA has been banned in Latvia since 14 November 2013.

The DEA announced its intent to schedule APINACA on 16 May 2013.

It is also banned in Germany as an Anlage II controlled drug.

APINACA is listed in the Fifth Schedule of the Misuse of Drugs Act (MDA) and therefore illegal in Singapore as of May 2015.