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- Lundmark, Jöns, et al.
(author)
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Paroxetine : pharmacokinetic and antidepressant effect in the elderly
- 1989
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In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 80:S350, s. 76-80
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Journal article (peer-reviewed)abstract
- To evaluate the pharmacokinetic properties, efficacy, and tolerability of paroxetine in elderly depressed patients, a clinical study was set up - initially at Aalborg Psychiatric Hospital in Denmark, and subsequently at the University Hospital in Linköping, Sweden. A total of 21 patients with a median age of 72 years were included in the study. After a single dose of 20 or 30mg of paroxetine followed by two drug-free days, treatment continued with 20 or 30mg daily for seven weeks. The majority of patients showed a continuous reduction in their HAMD scores, starting in the second week of treatment. Paroxetine was well tolerated at the doses given, and side-effects were mostly mild and transient. Steady-state, pre-dose plasma levels of paroxetine showed considerable variability, and the median steady-state concentration was higher in elderly patients compared with data from a previous study in young volunteers. Elimination half-lives also showed variability between these elderly patients, but tended to be longer after cessation of multiple dosing than after a single dose. They also tended to be longer than in the young volunteers. The results of this study do not advocate reduced doses of paroxetine in the elderly, but further studies are warranted.
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- Nordén, Bengt, 1945, et al.
(author)
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nteractions between DNA and Psoralenamines Studied with Dichroism Techniques
- 1986
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In: Photochemistry and Photobiology. - : Wiley. - 0031-8655 .- 1751-1097. ; 44:5, s. 587-594
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Journal article (peer-reviewed)abstract
- The interaction of a series of water-soluble mono- and bis-psoralenamines with calf thymus DNA has been studied with flow UV linear dichroism (LD), circular dichroism (CD) and equilibrium techniques. The positive charge of a protonated amino group strongly enhances the DNA affinity compared to that of the parent compound, 8-methoxypsoralen. The orientation of the psoralen when bound to DNA, depends on the position of the amino substituent. With amino substituents in the 5-position (on the‘hydrophobic edge’of psoralen) psoralenamines tend to bind with a considerable tilt relative to the average orientation of the DNA base-pairs. The tilt generally increases with an increased psoralen: base-pair ratio, indicating a more random, nonintercalated binding. With the amino substituents in the 8-position the psoralen binds with its plane parallel to that of the DNA bases as expected for intercalation. The DNA CD supports that these psoralenamines induce a considerable perturbation of the DNA structure, and the CD induced in the psoralen chromophore is in qualitative agreement with intercalation. The study also includes a theoretical and an experimental determination of the UV transition moments of the psoralen chromophore.
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