Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances.

Several experimental studies of pulmonary emphysema using animal models have been described in the literature. However, only a few of these studies have focused on the assessment of ergometric function as a non-invasive technique to validate the methodology used for induction of experimental emphysema. Additionally, functional assessments of emphysema are rarely correlated with morphological pulmonary abnormalities caused by induced emphysema.

Syntheses and binding studies of new [(aryl)(aryloxy)methyl]piperidine derivatives and related compounds as potential antidepressant drugs with high affinity for serotonin (5-HT) and norepinephrine (NE) transporters.

In a wide search program toward new, efficient, and fast-acting antidepressant drugs, we have prepared series of new compounds having an (aryl)(aryloxy)methyl moiety linked directly or through a methylene chain to different substituted and unsubstituted cycles (isoquinoline, piperazine, piperidine, tetrahydropyran, or cyclopentane). These compounds have been evaluated for their affinities for serotonin (5-HT) transporter (SERT) and 5-HT(1A) and 5-HT(2A) receptors. Racemic mixtures of 4-[(aryl)(aryloxy)methyl]piperidine derivatives showed much higher affinity values for SERT than fluoxetine and resulted in lack of affinity for 5-HT(1A) and 5-HT(2A) receptors.

Derivatives of (R)- and (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin: synthesis and interactions with 5-HT1A receptors.

Analogs of the 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin [(S)-1,(S)-UH301] have been prepared. The C8-substituent has been varied, and in some derivatives one of the N-propyl groups has been exchanged for a 4-(8-aza-7,9-dioxospiro[4.5]decan-8-yl)-butyl group.

Synthesis and pharmacology of the enantiomers of UH301: opposing interactions with 5-HT1A receptors.

The (S)-enantiomer of 5-fluoro-8-hydroxy-2-(dipropylamino) tetralin [(S)-2a; (S)-UH301] was the first reported 5-HT1A receptor antagonist. We now give a full account on the synthetic effort leading to the preparation of the racemate and the enantiomers of 2a. The crystal and molecular structure of 2a.

Development of tolerance to 8-OH-DPAT induced blockade of acquisition of a passive avoidance response.

We examined the effects of manipulating 5-HT1A receptors on the performance of a passive avoidance task in rats. Firstly, we studied the effect of racemic 8-OH-DPAT and compared it to the pure enantiomers (subcutaneous injection, s.c.