Antipsychotic agent

These drugs are usually used to treat patients with psychotic or other serious related illnesses. They have common side effects such as muscle spasms, restlessness, and Parkinsonism. However, these drugs are considered safe, because the side effects are transient. Clozaril, 77, is the 

Drugs Injectable Form Equivalent Dose (mg) Daily Dosage (mg) Sedation Incidence of Movement Disorders Anticholinergic Effects 

Note +++ = high ++ = moderate + = low - = not present. Dosages of oral medications only. 

Acetylcholine, an ester of choline and acetic acid, is synthesized in cholinergic nenrons according to the following scheme  

The acetylcholine, in turn, is hydrolyzed by both acetylcholinesterase and plasma butyrylcholinesterase. Choline is actively transported into nerve terminals (synaptosomes) by a high-affinity uptake mechanism. Furthermore, the availability of choline regulates the synthesis of acetylcholine 

FIGURE 12 Botulinum toxin causes skeletal muscle paralysis by binding to acetylcholine receptors on the motor end plate. 

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Two closely related indoles fused to an additional saturated ring have been described as CNS agents. The first of these is obtained in straightforward manner by Fischer indole condensation of functionalized cyclohexanone 0 with phenyl hydrazine (19). The product, cyclindole (21) shows antidepressant activity. The fluorinated analogue flucindole (26) can be prepared by the same scheme. An alternate route starting from a somewhat more readily available intermediate involves as the first step Fischer condensation of substituted phenyl hydrazine with 4-hydroxycyclohexanone (23). The resulting alcohol (24) is then converted to its tosylate (25). Displacement by means of dimethyl amine leads to the antipsychotic agent flucindole (26). ... 

Pi peridinobenzimidazole also serves as starting material for the antipsychotic agent halopemide (69). In the absence of a specific reference, one may speculate that the first step involves alkylation with bromochloro-ethane to give halide The chlorine may then be converted to the primary amine by any of several methods such as reaction with phthalimide anion followed by hydrazinolysis. Acylation with j -fluorobenzoyl chloride then gives the desired product. 

One of a variety of syntheses of the antipsychotic agent bro-foxine (50) begins with a Grignard reaction on methyl anthra-nilate. The resulting product ( ) is reacted with phosgene in pyridine and the synthesis is completed by bromination in acetic acid to give brofoxine. 

An antipsychotic agent with a chemical structure somewhat similar to that of tioperidone (59) is ket an serin (68). The synthesis involves the straightforward thermal alkylation of... 

Antidepressant agents show almost the same degree of tolerance as to the nature of the tricyclic moiety as do the antipsychotic agents. Thus the dehydration product(s) from the condensation of ketone 9 with the Grignard reagent from 3-chloroethyl-N, J -dimethylamine affords the antidepressant diothiepin (98). ... 

FIuorobutyrophenone derivatives of 4-aryl piperidines are well-known antipsychotic agents. It is thus interesting to note that the piperidine can in fact be fused onto an... 

The phenothiazine duoperone (5) combines structural elements found in phenothiazine and buty-rophenone antipsychotic agents. Alkylation of substituted piperidine 1 with 3-chloropropanol affords the intermediate 2 treatment of this with thionyl chloride converts the terminal hydroxyl to chloride. Alkylation of the phenothiazine 4 with halide 3 affords the antipsychotic agent duoperone (5) [1]. 

Alkylation of the dimethylpiperazine 12 with 3-chloropropanol followed by treatment of the product 13 with thionyl chloride gives the halide 14. Alkylation of the anion from carbazole (15) with that halide leads to the tricyclic antipsychotic agent rimcazole (16) [4]. 

Derivatives of 11 //-dibenz[6,e]azepine (morphanthridines) and 5/2-dibenz[Z>,/]azepine are valuable, commercial pharmaceutical products. The most important derivatives are the antidepressant, Depramine (16),30 the antiepileptic, Carbamazepin (17),62 the hypnotic agents Perlapine (18),63-64 and its 2-fluoro derivative (Fluperlapine),65 and Opipramol (19), an antidepressant and antipsychotic agent.66... 

Nightengale BS, Crumly JM, Liao J, et al (1998). Economic outcomes of antipsychotic agents in a medicaid population traditional gents vs risperidone. PsyehopharmacBullltAy 373—82. 

Although atypical antipsychotic agents may cost several times as much as traditional antipsychotics, drug costs in schizophrenia account for only 1-4% of the total treatment cost (Knapp, 1997). The argument then is that a small increase in drug costs— say to 10% of total cost—may result in disproportionate savings in the highly expensive direct hospital costs, if clinical trial... 

Chemical ionization can be used at ambient pressures. Chemical ionization was used in tandem MS, using a triple quadrupole instrument, to characterize the antipsychotic agent 2-amino-N(4-(4-(l,2-benzisothiazol-3-yl)-l-piperazinyl)butyl)benzamide from human plasma.5... 

Dear, G.J., Fraser, I.J., Patel, D.K., Long, J., and Pleasance, S., Use of liquid chromatography-tandem mass spectrometry for the quantitative and qualitative analysis of an antipsychotic agent and its metabolites in human plasma and urine, /. Chromatogr. A, 794, 27, 1998. 

Treatment of behavioral symptoms should begin with nonpharmacologic treatments, but may also include antipsychotic agents and/or antidepressants. 

Murray, M. (2006). Role of CYP pharmacogenetics and drug-drug interactions in the efficacy and safety of atypical and other antipsychotic agents. /. Pharm. Pharmacol, 58, 871— 85. 

Ring, B. J. et al. (1996). Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. /. Pharmacol. Exp. Ther., 276, 658-66. 

Roth, B. L., Craigo, S. C., Choudhary, M. S. etal. (1994). Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine- 6 and 5-hydroxytryptamine-7 receptors. /. Pharmacol. Exp. Ther., 268, 1403-10. 

Tran, P. T., Lawson, W. B., Andersen, S. et al. (1999). Treatment of the African American patient with novel antipsychotic agents. In J. M. Herrara, W. B. Lawson and J. J. Sramek, eds., Cross-Cultural Psychiatry. Sussex John Wiley Sons. 

Examples abound regarding the role of serendipity in the discovery of new therapeutic approaches, which on closer examination usually turned out to be the result of clinicians paying attention to unexpected clinical effects rather than discounting them. For example, lithium was tried first for hypertension, chlorpro-mazine was initially developed as an anesthetic, and imipramine was originally regarded as an antihistamine and an antipsychotic agent. Without astute clinical observations, these drugs would not have found their niche, nor would clozapine have been revived for the benefit of millions of the most difficult to treat schizophrenic patients. Other examples include the expanded indications of newer... 

In their synthesis of potential antipsychotic agent analogues, Navas et al. used 2-aminobenzene sulfonamide 30 to open the azoniaspirodecane bromide 29 (Equation 8) <1998BMC811>. 

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