Chlorpromazine base

Most substances have at least some degree of solubility in water and while they may appear to be insoluble by a qualitative test, their solubility can be measured and quoted precisely. In aqueous media at pff 10, chlorpromazine base has a solubility of 8 x 10 mol dm, that is it is very slightly soluble, but it might be considered to be insoluble if judged visually by the lack of disappearance of solid placed in a test-tube of water. 

Association is a feature of chlorpromazine base and related derivatives in the supercooled state.< Such associations may be preceded by the formation of intramolecular complexation, i.e., different regions of the same molecular species acting as donor and acceptor. It is interesting to note that in this context the solid state structure of chlorpromazine base is not symmetrical, presumably due to van der Waals or perhaps weak charge transfer interaction between the chlorine ring substituent and the side-chain amine group. Donor and acceptor properties can be modified by chemical substitution, and are sensitive to steric hindrance. In a way, intramolecular charge transfer reproduces the effect of delocalized electrons. ... 

FIGURE 7. (a) Spectra of chlorpro-mazine and of its iodine complex in the frequency range F = 3500-1200 cm Curve marked A refers to crystalline chlor-promazine at 20°C. Curve marked B refers to the iodine complex of chlorpromazine base at 20 °C. Curve marked C refers to chlorpromazine in the liquid state at 60°C. (b) Same as for Figure 7a but in the range 1300-400 cm T is transmittance in arbitrary units. 

The results of a pH 4-9.5 solubility assay of chlorpromazine are shown in Fig. 6.10. The horizontal line represents the upper limit of measurable solubility (e.g., 125 pg/mL), which can be set by the instrument according to the requirements of the assay. When the measured concentration reaches the line, the sample is completely dissolved, and solubility cannot be determined. This is automatically determined by the instrument, based on the calculated value of R. When measured points fall below the line, the concentration corresponds to the apparent solubility Sapp. 

The most dramatic effects are with the bases. The first seven bases in Table 7.19 are the most lipophilic. Cosolvent causes their %R to decrease, consistent with effect (2) listed above. For the three least-lipophilic bases, %R increases with cosolvent, consistent with effect (1). Chlorpromazine and verapamil experience... 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. The choice of specific agent should based on patient specific factors, including potential for adverse drug reactions, and cost. SSRIs are effective for breakthrough nausea and vomiting but they are not superior to the less expensive antiemetics above. 

These medications cannot be dosed solely based on their dopamine receptor blocking potency, because they also have effects on other receptors that must be factored into their dosing (see Table 4.6). For example, it is not unusual to begin treatment of a psychotic patient with a 5 mg dose of haloperidol. In terms of dopamine receptor blocking potency, 5 mg of haloperidol is more or less equivalent to 500 mg of chlorpromazine. If a patient were immediately treated with 500 mg of chlorpromazine, however, he/she would likely have side effect problems such as dizziness and excessive sedation. This is because the medications with the lowest dopamine receptor blocking potency are the most potent at other receptor systems responsible for these side effects. (See Table 4.7) The evolution of antipsychotics from low to medium to high potency has been driven not only by the desire to find... 

CHLORPROMAZiNE Individualize dosage based on condition severity. Increase dosage until symptoms are controlled, then gradually reduce dosage to the lowest effective maintenance level. Increase parenteral dosage only if hypotension has not occurred. 

The melting range reported for chlorpromazine free base is 56-58°C [5], while the melting range of chlorpromazine hydrochloride has been reported to be 195-198 [8]. 

The boiling range reported for chlorpromazine free base is 200-205°C [5]. 

The mass spectrum of chlorpromazine hydrochloride was obtained using a Shimadzu PQ-5000 mass spectrometer [13], In this study, the parent ion was collided with helium as the carrier gas, and an ionization beam energy of 70 eV was used. The mass spectrum thusly obtained is presented in Figure 7. The molecular ion peak was observed at m/z = 318.2, and the base peak was at m/z = 58.2. Assignments for the fragmentation pattern, the peak relative intensities, and the proposed structures are found in Table 5. 

Bhatt et al. have described a method based on the complex formation between chlorpromazine and K3Fe(CN)5 [151]. The latter substance yielded a reduction wave at zero applied potential, and addition of chlorpromazine decreased the wave height in an amount directly proportional to the amount added. Optimum conditions for the determination were reported to be pH 7.4-6.2, use of 0.1 M KCl as the supporting electrolyte, and 0.001% methyl red solution as the maximum suppressor. In this system, chlorpromazine can be determined up to concentrations of 1.4 pg/mL. 

Wang and Freiha have designed a carbon-paste electrode, based on a piston principle that enables an outer layer of paste to be extruded and removed, and used this in investigating possible extractive accumulation and further characteristics of the pre-concentration step in voltammetric analysis [163]. Chlorpromazine was used as a model compound. 

A simultaneous fluorimetric determination of chlorpromazine and promethazine has been reported [143]. The method was based on the fact that in media of different pH, the photochemical conversion of chlorpromazine and promethazine into a fluorescent product varies. 

A gravimetric assay method based on the precipitation of chlorpromazine hydrochloride in hulk and in various dosage forms has been reported [179]. The method uses a KBrO-KBr mixture in the presence of 15%... 

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