Butyrophenone neuroleptic

A. Katsifis, K. Hamacher, J. Schnitter, G. Stdcklin, Optimization studies concerning the direct nucleophilic fluorination of butyrophenone neuroleptics, Appl. Radiat. Isot. 44 (1993) 1015-1020. 

K. Hamacher, W. Hamkens, Remote-controlled one-step production of F-18 labeled butyrophenone neuroleptics exemplified by the synthesis of nca [F-18]N-methylspi-perone, Appl. Radiat. Isot. 46 (1995) 911-916. 

C. Shiue, J.S. Fowler, A.P. Wolf, M. Watanabe, C.D. Arnett, Synthesis and specific activity determination of NCA F-labeled butyrophenone neuroleptics Benperidol, haloperidol, spiroperidol and pipamperone, J. Nucl. Med. 26 (1985) 181-186. 

The choreiform movements and behaviors can be only partially controlled by phenothiazines or butyrophenone neuroleptics. 

The synthesis of fluorine-18-labelled receptor-based radiopharmaceuticals carried out before 1986 have been reviewed331 and the methods applied for the synthesis of 18F-butyrophenone neuroleptics such as spiroperidol (spiperone), haloperidol have been critically evaluated. The synthesis for preparing 7V-(2-[18F]fluoroethyl)spiperone330 involving the [18F]fluoride ion displacement of a suitable leaving group on the ethyl side chain was found to be particularly good (>50% yield). 

Haloperidol is a butyrophenone neuroleptic drug. The enzymes involved in its biotransformation include oxidative cytochrome P450 isozymes, carbonyl reductase, and uridine diphosphoglucose glucuronosyltransferase (1). It is mainly cleared by glucuronidation. 

Binding studies with tritiated neuroleptics have established the existence of two types of central DA receptors D[ and D2 their numbers and ratios vary in brain areas. Most interesting, however, is that both are altered in drug-naive schizophrenics. Emphasis has concentrated on the D2 subtype that seems implicated in the observable clinical responses. The role of the postsynaptic Dt receptor is not clear. It is known, however, that even though neuroleptic drugs are D,/D2 antagonists, in vitro D2 effects are achieved at 103 lower concentrations. D2 receptors are also located in central areas outside the BBB. One is the CTZ in the medulla. Presynaptic stimulation, which leads to DA inhibition there, may be the reason that many of the phenothiazine and butyrophenone neuroleptic drugs also excel as antiemetics (see comments, Table 12-11). It also explains why several DA2... 

Curry, S.H. Brown, E.A. Hu, O.Y.-R Perrin, J.H. Liquid chromatographic assay of phenothiazine, thiox-anthene and butyrophenone neuroleptics and antihistamines in blood and plasma with conventional and radial compression columns and UV and electrochemical detection. J.Chromatogn, 1982, 231, 361-376... 

Chlorpromazine, haloperidol, and other phenothiazine and butyrophenone neuroleptics produce significant blockade of both a and D2 receptors (see Chapter 18). 

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