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Otis LS, Pryor GT, Marquis WJ, Jensen R, Petersen K.
“Preclinical Identification Of Hallucinogenic Compounds”.
Pharmacology of Hallucinogens. 1978;p126-149.
New compounds are being synthesized daily for both medicinal and research purposes. Lacking are reliable preclinical tests for identifying possible hallucinogenic activity in new compounds. As mentioned recently by several authors (Dixon, 1968; Brawley and Duffield, 1972; Silva and Cahil, 1975; Shah et al., 1975), this lack requires remedy. We undertook to meet this need under a contract from the National Institute on Drug Abuse (NIDA). The rationale not establishing discriminative tests for hallucinogens include the following: 1. The hallucinogenic drug-induced state in humans resembles that manifested during the acute phases of psychotic episodes in many ways. Thus, the identification of hallucinogenic compounds specifically synthesized for theoetical purposes and the subsequent elucidation of their mechanisms of action could be useful to researchers attempting to determine the etiology of certain mental illnesses. Indeed, several theories have been suggested purporting tha abnormal production or metabolism of endogenous putative central neurotransmitters yielding hallucinogenic compounds may be responsible for the onset and maintenance of aberrant mental function. For example, Saavedra, Liz and Axelrod (1972) demonstrated that the human brain is capable of synthesizing hallucinogenic compounds by way of N-methylation of endogenous tryptamines to yield DOT and bufatenin--compounds that have been reported to be present in the urine of schizophrenic patients (Tanimokai et al., 1967). 2. The ability to differentiate between the hallucingoenic properties of CNS drugs and those characteristically induced by other agents would aid in evaluating theories purporting a continuum of CNS excitable states. These theories hypothesize that hallucinogens induce a hyperexcited brain syndrome localized on a continuum between stimulant activation anti frank epileptiform seizures (Winters and Wallach, 1970; Fischer, 1971). 3. Pharmaceutical houses would benefit from a battery of preclinical tests that would reliably identify hallucinogenic properties of psychoactive drugs since these properties would render an otherwise promising compound nonmarketable. The overall goal of this research was to select-- on the basis of a review of the literature and other sources-- the fewest, simplest, most economical preclinical tests tht would reliably identify compounds with hallucinogenic acitivity and to validate these test procedures in our laboratory. Since several of the newer hallucinogens are amphetamine derivatives, we concentrated on identifying preclinical tests that discriminated such compounds, as well as the classic hallucinogens, from classic stimulants.
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