Psychotropic Compounds

The first agent of this class to be introduced in the clinic, haloperidol (18-8), interestingly shares the 4-phenylpiperidine structural fragment found in the central analgesic agent meperidine and its derivatives (see Chapter 7). The former compound may well have been discovered in the course of further SAR studies on the opiate [20]. An unusual synthesis of haloperidol starts with the product (18-1) from Friedel-Crafts acylation of 4-fluorobenzene with succinic anhydride. Successive protection of the 

Alkylation of the basic amino group in (19-6) with butyrophenone (20-1), available from the acylation of fluorobenzene with 4-chlorobutyryl chloride, affords the antipsychotic drug droperidol (20-2) [21]. Alkylation of the fully reduced intermediate (19-7) with a side chain (20-3) yields pimozide (20-4) [22]. 

The presence of a quaternary carbon atom at the 4 position of the piperidine in the form of a spiro substituent seems to enhance potency. The starting piperidin is the product from the formal additon of cyanide and aniline to the 4 position of A-benzyl-4-piperidone (see Chapter 7 [28-3] for preparation). Reaction of that with formamide serves to form the spiro-imidazoline ring (21-4). The benzyl protecting group is then removed by hydrogenolysis over palladium to give the secondary 

Yet another piperidine-based antipsychotic agent replaces the butyrophenone or diarylpropyl function found in earlier compounds by a benzopyrimidine group. The synthesis starts by the conversion of the carboxylic acid in piperidine (22-1) to its acid chloride. Reaction with 1,3-difluorobenzene (22-2) in the presence of aluminum chloride affords the acylated product (22-3). Reaction with hydroxylamine leads to the corresponding oxime (22-4). Treatment of that derivative with a base 

---

Violland, R., Violland-Duperret, N., Pacheco, H., Trouiller, G., and LeBlanc, A. (1971) Potential psychotropic compounds. VIII. Synthesis and pharmacological activity of 2-aminotetralins related to psychotomimetics. Bull. Chim. Ther., 6 196-202. 

Besides the group of psychotropic compounds, we must quote here the antibiotics as drugs where a rapid recent development of techniques can be observed. D.c. polarographic techniques for the determination of chloramphenicol [242], tetracycline [243] and streptomycin [244] are available. The polarographic determination of penicillin G potassium salt is only indirect and is preceded by the introduction of a nitroso group [245]. The synthesis of chloramphenicol comprises the chemical reduc-... 

Wurst, M., Semerdzieva, M. Vokoun, J. (1984). Analysis of psychotropic compounds in fungi of the genus Psilocybe by reversed phase high-performance liquid chromatography. Journal of Chromatography, 286, 229-235. 

A number of excellent review articles exist, including several that explain MR spectroscopy and detail the impact of MR spectroscopy in drug design and in preclinical studies, and others that provide overviews of human in vivo metabolism and pharmacokinetics measured by 19F MR in fluoropyrimidine compounds as well as in psychotropic compounds [1, 3-5, 7-10, 59, 60-63], In keeping with other facets of drug development, the number of 19F MR clinical investigations is much smaller than the number of animal model, specimen, cell line, or solution experiments. 

Conversely, long-term accumulation of tecastemizole in the liver was not found. After 8 days of tecastemizole treatment at a daily dose of 27Qmg, 19F MR signal was found in the livers, but not the hearts, of healthy volunteers with a concentration range of 2-30 pM [11], In contrast to the psychotropic compounds, no fluorine signal was found in the liver after 28 days of washout, suggesting that tecastemizole and its fluorinated metabolites were eliminated from liver. 

CYP2C19 has also been shown to exhibit polymorphic variability and is thought to be under primary genetic control (Bertilsson et al. 1989). This enzyme is involved in the metabolism of a number of different psychotropic compounds, such as tricyclic antidepres-... 

In the last two decades, several clinical studies have focused on Hispanics and their response to psychotropic compounds. These studies are summarized here and the findings are reexamined, taking into account the expanded ethnopsychopharmacological knowledge base outlined earlier. 

Cummings JL. Cholinesterase inhibitors A new class of psychotropic compounds. Am J Psychiatry 2000 157 4-15. 

The structure of harmine was known by this time (Fischer 1899 Perkin Robinson 1919A Perkin Robinson 19193), and the compound had been synthesized in 1927 (Manske etaL 1927 Spath Lederer 1930A Spath Lederer 19303). In 1957, Hochstein and Paradies isolated from Peruvian B. caapi harmine as well as harmaline and i leptaflorine or tetrahydroharmine (Hochstein Paradies 1957). These compounds were also found in an ayahuasca potion from Peril, and harmaline and (sf-leptaflorine (TetraHydroHarmine) were proposed to be psychotropic compounds in this ayahuasca potion. In 1969, the stable P-carboline alkaloid harmine was found in quantities similar to fresh material in Spruce s original type collection of Banisteriopsis caapi from 1852 (Schultes etaL 1969) Rivier and Lindgren found the same three p-carbolines as major alkaloids of Banisteriopsis caapi (Rivier Lindgren... 

Single Convention on Narcotic Drugs, 1961 as amended by the 1971 Protocol concerning psychotropic compounds. 

Psychotropic compounds, such as caffeine and nicotine, can exist in air as a result of their release in tobacco smoke or when certain drugs or essences are inhaled as vapors. These psychotropic substances belong to various classes of organic compounds with different physico chemical properties and different routes of release into the environment, so they may exist in the gaseous or asparticulates and as native compounds or derivatives. For instance, nicotine is mostly gaseous when it is a free base, but combines with tobacco smoke particles when in acidic form (Liang and Pankow, 1996). Cocaine and heroin in the atmosphere presumably exist mainly as solid particulates (Dindal et al., 2000 Cecinato and Balducci, 2007). 

The first observation of illicit drugs in the atmosphere was unexpected and occurred in a study with quite different goals. Thus, a preliminary objective of a subsequent study was to confirm the presence of these substances in air. Afterward, dedicated procedures were optimized to monitor psychotropic substances and drug residues in air with good precision and accuracy. The determination of psychotropic compounds in air is quite complex. Both air and airborne particles comprise thousands of... 

Diazepam use may be vulnerable to selfadjustment of dosage because of its capacity to produce immediate positive effects. This capacity is found similarly in addicting substances but not in non-addicting psychotropic compounds. This study was retrospective and uncontrolled and, as the authors indicate, cannot be considered as conclusive. Nevertheless, it certainly suggests strongly that benzodiazepine dependence occurs more frequently than has been recognized. 

---