This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The United States Drug Enforcement Administration (DEA) often discovers unidentified chemical substances during otherwise routine drug busts. Usually, these substances turn out to be chemical intermediates in the synthesis of known drugs. On some occasions, however, these substances turn out to be novel drugs of unknown pharmacology. Over the past few years, the majority of such novel drugs have turned out to be compounds of mixed action more specifically, they have some properties of stimulants, and some properties of hallucinogens. It thus appears that illicit chemists are attempting to capitalize on the popularity of the drug 3,4-methylenedioxymethamphetamine (MDMA, or Ecstasy) the protypical mixed action drug of abuse. These studies assay novel DEA compounds for stimulant and hallucinogen activity in mice. Stimulant activity will be assessed by quantification of locomotor activity following drug injection. Hallucinogen activity will be determined by quantification of a drug-elicited head twitch response. Both measures will be assayed simultaneously, in each mouse studied. We will study a series of chemically-related drugs according to the previously mentioned procedures. This will allow for determination of a structure-activity relationship with this type of drug. In other words, it may be the case that the simplest molecule in the series will be primarily a behavioral stimulant (i.e., it will increase locomotor activity without inducing head twitch behavior.) Adding chemical substituents to this simple structure may imbue the resultant compound with hallucinogen activity (i.e., the new compound will continue to produce hyperlocomotion, but will also induce the head twitch response.) These data can thus be used by DEA in concert with the Analogue (Designer Drug) Act of 1986 to schedule and regulate these particular compounds, as well as all unknown and yet-to-be-synthesized compounds with similar structures.
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