Spectroscopic properties of neuroleptics: IR and Raman spectra of Risperidone (Risperdal) and of its mono- and di-protonated forms.
ABSTRACT Structures and IR and Raman spectra of Risperidone in its neutral, mono- and di-protonated forms were calculated in gas phase by DFT-B3LYP/6-31G* level. Mono-protonation occurs at the nitrogen atom of the piperidine ring, while nitrogen atom of the pyrimidine ring is the preferred site for the second protonation. The lowest-energy structure of the mono-protonated Risperidone is characterized by formation of a strong seven-membered O(pyrimidine ring)⋯(+)H-N(piperidine ring) intramolecular hydrogen-bonded cycle. In the high-energy spectral region (3500-2500 cm(-1)), the bands of the N-H(+) stretches and the changes in wavenumbers and IR intensities of the C-H stretches near to the piperidine nitrogen atom (Bohlmann effect) are potentially useful to discriminate conformations and protonation states. Di-protonated structures can be identified by the presence of an isolated absorption peak located in the low-energy IR region (660-690 cm(-1)), attributed to the out-of-plane N-H(+)(pyrimidine ring) bending deformation. The most intense Raman band of neutral Risperidone placed at ca. 1500 cm(-1), assigned to C=C(pyrimidine ring) stretch + C=N(pyrimidine ring) stretch, can be a useful vibrational marker to distinguish the neutral from the protonated forms.
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ABSTRACT: Previously, clinicians worked with antipsychotic drugs that almost invariably caused extrapyramidal side effects (EPS) at the dose at which they were clinically effective. By definition, all newer generation atypical antipsychotic agents are significantly better than conventional agents with regard to EPS; i.e., they are clinically effective at doses at which they do not cause EPS. This EPS advantage of atypical antipsychotics translates into several important clinical benefits, including better negative symptom efficacy, lesser dysphoria, less impaired cognition, and a lower risk of tardive dyskinesia; in fact, this "EPS advantage" is the principal basis of the many clinical advantages provided by the class of atypical antipsychotics. While all atypical agents share this "EPS advantage," there are important differences between these agents with regard to the ease and consistency with which this EPS advantage can be realized. Pharmacologically, different atypical antipsychotics differ; these differences translate into differences in their side effect profiles. Five atypical antipsychotics are currently available: clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. Meaningful differences between these agents with regard to weight gain, sedation, anticholinergic side effects, cardiovascular issues, endocrine side effects, hepatic and sexual issues, will be considered and their clinical implications discussed.Psychiatric Quarterly 02/2002; 73(4):297-311. · 1.26 Impact Factor