In a previous paper the theory of the new molecular descriptors called GETAWAY (GEometry, Topology, and Atom-Weights AssemblY) was explained. These descriptors have been proposed with the aim of matching 3D-molecular geometry, atom relatedness, and chemical information. In this paper prediction ability in structure-property correlations of GETAWAY descriptors has been tested extensively by analyzing the regressions of these descriptors for selected properties of some reference compound classes. Moreover, the general performance of the new descriptors in QSAR/QSPR has been evaluated with respect to other well-known sets of molecular descriptors.

Structure/Response Correlations and Similarity/Diversity Analysis by GETAWAY Descriptors. 2. Application of the Novel 3D Molecular Descriptors to QSAR/QSPR Studies

We present a new descriptor named signature based on extended valence sequence. The signature of an atom is a canonical representation of the atom's environment up to a predefined height h. The signature of a molecule is a vector of occurrence numbers of atomic signatures. Two QSAR and QSPR models based on signature are compared with models obtained using popular molecular 2D descriptors taken from a commercially available software (Molconn-Z). One set contains the inhibition concentration at 50% for 121 HIV-1 protease inhibitors, while the second set contains 12865 octanol/water partitioning coefficients (Log P). For both data sets, the models created by signature performed comparable to those from the commercially available descriptors in both correlating the data and in predicting test set values not used in the parametrization. While probing signature's QSAR and QSPR performances, we demonstrates that for any given molecule of diameter D, there is a molecular signature of height h </= D+1, from which any 2D descriptor can be computed. As a consequence of this finding any QSAR or QSPR involving 2D descriptors can be replaced with a relationship involving occurrence number of atomic signatures.

The signature molecular descriptor. 1. Using extended valence sequences in QSAR and QSPR studies.

Changes in body temperature after administration of adrenergic and serotonergic agents and related drugs including antidepressants: II.

The steady-state plasma concentrations of antipsychotic drugs show large interpatient variations but remain relatively stable from day to day in each individual patient. Monitoring of antipsychotic drug concentrations in plasma might be of value provided the patients are treated with only 1 antipsychotic drug. Some studies have reported a relationship between therapeutic response and serum antipsychotic drug 'concentrations' as measured using the radioreceptor assay (RRA) method, which measures dopamine receptor-blocking activity in plasma. Most studies, however, have failed to demonstrate such a relationship, and the RRA does not seem to provide the generally useful tool for plasma concentration monitoring of antipsychotic drugs that was hoped for initially. A lack of correlation between dopamine receptor-blocking activity in plasma and therapeutic response may be due to differences in the blood-brain distribution of both antipsychotic drugs and their active metabolites. Chemical assay methods (e.g. GLC and HPLC) have been used in studies which examined the relationships between therapeutic response and antipsychotic drug concentrations in red blood cells and in plasma. It seems that for these drugs, measuring red blood cell concentrations does not offer any significant advantage over measuring plasma concentrations. Reasonably controlled studies of plasma concentration-response relationships using randomly allocated, fixed dosages of chlorpromazine, fluphenazine, haloperidol, perphenazine, sulpiride, thioridazine and thiothixene have been published but often involve relatively few patients. A correlation between therapeutic response and plasma concentrations of thioridazine and its metabolites has not been demonstrated, and plasma level monitoring of thioridazine and its metabolites therefore appears to have no clinical value. Clinical behavioural deterioration concomitant with high plasma concentrations of chlorpromazine and haloperidol have been reported. A dosage reduction might be considered after 2 to 4 weeks' treatment in non-responders who have plasma chlorpromazine concentrations above 100 to 150 micrograms/L or plasma haloperidol concentrations above 20 to 30 micrograms/L. Non-responders and good responders to chlorpromazine treatment, however, have plasma drug concentrations in the same range, and a therapeutic range of plasma chlorpromazine levels has not been defined. Therapeutic plasma haloperidol concentrations (i.e. 'window') in the range of 5 to 20 micrograms/L have been reported by some investigators, but others have found no such relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasma level monitoring of antipsychotic drugs. Clinical utility.

. The pain of infiltrating lidocaine with epinephrine into skin is reduced by the addition of sodium bicarbonate. The effect of varied concentrations of sodium bicarbonate on pain of infiltration of 1% lidocaine with epinephrine 1:100,000 was measured. Sodium bicarbonate at 40 and 100 meq/L of anesthetic solution caused significantly less pain than did 0 or 10 meq/L. The stability of epinephrine in a solution at pH 7.3 was also determined. Epinephrine concentration declined approximately 25% per week in anesthetic solution containing 100 meq/L sodium bicarbonate.

Neutralized Lidocaine with Epinephrine for Local Anesthesia

Analysis of blood and liver (when available) was conducted on five post mortem cases in which the decedant had a history of ingestion of thioridazine. Thioridazine (thior) and its metabolites: mesoridazine, thioridazine-sidechain sulfoxide or thioridazine-2-sulfoxide (T-S-SO); sulforidazine, thioridazine

Eric C. Juenge

Papers

Thioridazine and its Metabolites in Post Mortem Blood, Including Two Stereoisomeric Ring Sulfoxides

Synthesis, Isolation, and Characterization of Two Stereoisomeric Ring Sulfoxides of Thioridazine

Analysis of Drug Contamination from Parabens in Theophylline Olamine

High-performance liquid chromatographic determination of d-/l-epinephrine enantiomer ratio in lidocaine-epinephrine local anesthetics.

Decomposition of aminophylline in suppository formulations