Biomedical subjects
J Cutts
Publications and source records attributed to J Cutts.
A new approach to the design of sigma-2-selective ligands: synthesis and evaluation of N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)ethylamine-related polyamines at sigma-1 and sigma-2 receptor subtypes.
A series of polyamines based on the high affinity sigma receptor ligand N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) were developed and evaluated for their binding characteristics at sigma-1 and sigma-2 receptor subtypes. The data indicated that a considerable degree of structural variation is possible while still retaining nanomolar affinity at sigma receptors. As the structure of the polyamines was varied, their binding at sigma-1 and sigma-2 subtypes showed quite different and in some cases opposite trends, supporting the belief that these are pharmacologically distinct entities. Polyamines containing two nitrogen atoms showed optimal binding at both sigma-1 and sigma-2 receptor subtypes. Although additional nitrogen atoms resulted in decreased affinity at sigma-1 and sigma-2 subtypes, an increase in selectivity for sigma-2 subtypes was evident; the parent 3 showed greater selectivity for sigma-1 subtypes. Internitrogen spacings had a large effect on binding affinity and subtype selectivity. For example, the difference between N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4-dichlorobenzyl)-N,N'- dimethylethylenediamine (8) [K(i) = 29.9 nM at sigma-1 receptor and 18.3 nM at sigma-2 receptor] to N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4-dichlorobenzyl)- N,N'-dimethylethylenediamine (10) [K(i) = 1.49 nM at sigma-1 receptor and 12.1 nM at sigma-2 receptor] illustrates the importance of internitrogen spacing. Triamines 11 and 13 [Ki(sigma-2)/K(i)(sigma-1) = 0.19 and 0.10, respectively] containing the N-N-N-Ar spacings 3-3-2 and 4-4-2, proved to be the most sigma-2 subtype selective of the 15 polyamines examined in this study. The N-N-N spacings appear to be an important factor in their sigma-2 subtype selectivity. These compounds will serve as templates in the design of still further sigma-2 subtype selective ligands. The pyrrolidine ring (present in most of the polyamines tested in this series) proved to be an important recognition site for sigma receptor binding activity. Furthermore, alkyl substitution also appears to be important since the stripped down polyamines N-[2-(3,4-dichlorophenyl)ethyl]ethylenediamine (15) and N1-[2-(3,4-dichlorophenyl)ethyl]diethylenetriamine (16) exhibited relatively low binding affinity.
Psychometric properties of the revised UCLA Loneliness Scale and two short-form measures of loneliness in Zimbabwe.
The cross-cultural reliability in Zimbabwe of the Revised University of California at Los Angeles (UCLA) Loneliness Scale and two short forms of the Revised UCLA Loneliness Scale were investigated. Subjects comprised a sample of 1,354 adolescents and another sample of 754 adults. The reliability of the Revised UCLA Loneliness Scale was acceptable. The internal consistency of an eight-item short form of the Revised UCLA Loneliness Scale was adequate, but the reliability of a four-item short form was low. Factor analysis of the Revised UCLA Loneliness Scale, which yielded two factors similar to those reported in North America by Zakahi and Duran (1982) supported the construct validity of the Revised UCLA Loneliness Scale in Zimbabwe. The Revised UCLA Loneliness Scale and the eight-item short form were highly correlated, but this association was spuriously elevated by the fact the eight-item short form is part of the full scale. Factor analysis of the eight-item short form suggested that this scale does not consistently reflect the factor structure of the full scale. We concluded that the Revised UCLA Loneliness Scale possesses acceptable reliability and factorial validity in Zimbabwe and that the eight-item version is superior to the four-item form of the Revised UCLA Loneliness Scale as a short loneliness measure. However, additional refinements may be needed to further improve the eight-item short version.
Stimulation by vasopressin and alpha-catecholamines of phosphatidylinositol formation in isolated rat liver parenchymal cells.
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