/sup 13/C NMR studies of the molecular flexibility of antidepressants

Journal Article · Sat Feb 01 00:00:00 EST 1986 · J. Pharm. Sci.; (United States)

DOI:https://doi.org/10.1002/jps.2600750206· OSTI ID:5811221

Munro, S L; Andrews, P R; Craik, D J; Gale, D J

The solution dynamics of a series of clinically potent antidepressants have been investigated by measuring /sup 13/C NMR relaxation parameters. Correlation times and internal motional rates were calculated from spin-lattice relaxation times and nuclear Overhauser effects for the protonated carbons in mianserin, imipramine-like antidepressants, and amitriptyline-like antidepressants. These data were interpreted in terms of overall molecular tumbling, internal rotations, and inherent flexibility of these structures. Of particular interest was the conformational variability of the tricyclic nucleus of the tricyclic antidepressants, where the data indicated a fivefold difference in mobility of the dimethylene bridge of imipramine-like antidepressants relative to amitriptyline-like compounds. The implications of such a difference in internal motions is discussed in relation to previous NMR studies and to the reported differences in pharmacological activity of these antidepressants.

• Research Organization: Victorian College of Pharmacy, Ltd., Parkville, Australia
• OSTI ID: 5811221
• Journal Information: J. Pharm. Sci.; (United States), Vol. 2
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTIDEPRESSANTS
MOLECULAR STRUCTURE
CARBON 13
FLEXIBILITY
NUCLEAR MAGNETIC RESONANCE
OVERHAUSER EFFECT
SOLVENTS
SPIN-LATTICE RELAXATION
TRACER TECHNIQUES
WATER
CARBON ISOTOPES
CENTRAL NERVOUS SYSTEM AGENTS
DRUGS
EVEN-ODD NUCLEI
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MECHANICAL PROPERTIES
NUCLEI
OXYGEN COMPOUNDS
PSYCHOTROPIC DRUGS
RELAXATION
RESONANCE
STABLE ISOTOPES
TENSILE PROPERTIES
550201* - Biochemistry- Tracer Techniques