paroxetine, Paxil
Aggressive behaviour and platelet 3H-paroxetine binding in schizophrenia.

Maguire K, Cheung P, Crowley K, Norman T, Schweitzer I, Burrows G.

Department of Psychiatry, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.

Forty schizophrenic patients were included in a study of the relationship between serotonin function as measured by 3H-paroxetine binding to platelet membranes and aggressive behaviour. Patients classified as either aggressive or non-aggressive were paired by age, sex and duration of illness. 3H-Paroxetine binding variations were avoided by taking samples for each pair between 09:00 and 11:00 h, within 4 days of each other, and by assaying pair of samples together. The mean Kd for the aggressive group was 0.193 +/- 0.126 nM and the mean Kd for the non-aggressive group was 0.176 +/- 0.164 nM. The mean Bmax for the aggressive group was 1451 +/- 386 fmol/mg protein while the mean for the non-aggressive group was 1549 +/- 375 fmol/mg protein. There was no significant difference between the groups for either parameter, Kd or Bmax. There were no significant correlations between psychopathology rating including positive and negative symptoms, depression, suicidal thoughts, impulse control, as well as both past and present history of aggression, hostility and irritability traits, psychopathic deviance and either Bmax and Kd. This study finds no relationship between aggressive behaviour and peripheral serotonin function as measured by 3H-paroxetine binding to platelet membranes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9050129&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike?

Sanchez C, Meier E.

H. Lundbeck A/S, Copenhagen-Valby, Denmark.

The behavioral profiles of five clinically used selective serotonin reuptake inhibitors (SSRIs) citalopram, paroxetine, sertraline, fluvoxamine and fluoxetine, have been compared in animal models of antidepressant (mouse forced swim test), anxiolytic (exploration of black and white test box and foot-shock-induced ultrasonic vocalization in the rat) and antiaggressive (isolation-induced aggressive behavior in the mouse) activity. the results are discussed in relation to receptor binding data from the literature. Furthermore, affinities for the sigma 1 and sigma 2 binding sites are presented. Citalopram reversed the immobility induced by forced swimming with a potency similar to that of imipramine. Paroxetine, fluvoxamine and fluoxetine reversed swim-induced immobility less potently and with a maximum of 40-50% reversal. Citalopram produced a mixed anxiogenic-/anxiolytic-like response in rats tested in the two-compartment black and white box. Paroxetine induced an anxiogenic-like response at low doses and the other SSRIs were without major effects. Citalopram and paroxetine inhibited footshock-induced ultrasonic vocalization with high potencies. The dose-response curve was biphasic for citalopram with a maximum of 64% inhibition. Sertraline and fluvoxamine inhibited the vocalization less potently, and fluoxetine induced a weak inhibitory effect corresponding to a maximum of 32%. Sertraline, fluvoxamine and fluoxetine inhibited isolation-induced aggressive behavior, whereas citalopram and paroxetine were inactive. Both 5-HT1 and 5-HT2 receptors are involved, and there was a functional interaction between 5-HT1A and 5-HT2A or 5-HT2C receptors, as ritanserin potentiated the antiaggressive effect of 1,5-HTP as well as that of 8-OH-DPAT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9084057&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Regional distribution of specific high affinity binding sites for 3H-imipramine and 3H-paroxetine in human brain.

Rosel P, Menchon JM, Oros M, Vallejo J, Cortadellas T, Arranz B, Alvarez P, Navarro MA.

Hormone Unit, Hospital Princeps d'Espanya, Barcelona, Spain.

The binding of 3H-paroxetine and 3H-imipramine has been compared in 17 different regions of 12 human control brains. Our findings reveal that the regional distribution is similar for both radioligands and their bindings tend to be parallel in the brain. The highest binding site density was found in basal ganglia (hypothalamus Bmax 780 +/- 102 fmol/mg protein for 3H-imipramine binding and Bmax 515 approximately 83 for 3H-paroxetine binding). The lowest values were found in cortical areas (cingulate cortex 191 +/- 18.5 fmol/mg for 3H-imipramine binding and 88 +/- 7.5 fmol/mg for 3H-paroxetine binding). The Kd values for 3H-paroxetine binding to neuronal membranes were similar in all brain regions (mean +/- s.d. Kd 0.07 +/- 0.007 nM) and also for 3H-imipramine binding (mean +/- s.d. Kd 1.05 +/- 0.12 nM). As these values are the same as in platelet membrane, the results obtained indicate that both binding sites are identical in neuronal and in platelet membranes. These findings suggest that both ligands are good markers of the 5HT transporter. However, the higher affinity of 3H-paroxetine confirms that this compound is a better radioligand for the 5HT uptake site.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9085196&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Decreased platelet 3H-paroxetine binding in obsessive-compulsive patients.

Marazziti D, Rossi A, Gemignani A, Giannaccini G, Pfanner C, Milanfranchi A, Presta S, Lucacchini A, Cassano GB.

Istituto di Psichiatria, Universita di Pisa, Italia.

The similarities between the serotonin (5-HT) transporter in both human platelets and human brain permit us to investigate this structure in patients with different psychiatric disorders. Several reports have shown abnormalities of the 5-HT transporter, by means of the measurement of the 5-HT uptake or of the 3H-imipramine binding, in platelets of patients with obsessive-compulsive disorder (OCD). The availability of the ligand 3H-paroxetine, a selective 5-HT reuptake inhibitor, to label the 5-HT transporter, promoted us to evaluate the binding of 3H-paroxetine in platelets of 18 drug-free patients with OCD. The results, showing that the patients had a lower number of 3H-paroxetine sites, which is inversely correlated with the Yale Brown Obsessive-Compulsive Scale total score, than a similar group of controls, add supporting evidence to the involvement of 5-HT in OCD. In addition, the decreased functionality of the 5-HT transporter seems to be linked to the severity of OC symptoms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9121618&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Synergism of 5-HT 1B/D antagonists with paroxetine on serotonin efflux in rat ventral lateral geniculate nucleus slices.

Davidson C, Stamford JA.

Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, UK.

Serotonin (5-HT) efflux in rat ventral lateral geniculate nucleus (vLGN) slices was evoked by electrical stimulation (20 pulses at 100 Hz, 10 mA, 190 ms train) and measured, along with 5-HT uptake, by fast cyclic voltammetry at implanted carbon fibre microelectrodes. Paroxetine (100 nM), a selective serotonin reuptake inhibitor (SSRI), increased stimulated 5-HT efflux to 194 +/- 25% of pre-drug values at maximum (mean +/- SEM, n = 5) and the half-life of uptake to 684 +/- 135%. When given alone, neither the selective 5-HT 1B antagonist isamoltane (1 microM) nor the 5-HT 1D/B antagonist GR 127935 (50 nM), affected 5-HT efflux or uptake under this stimulation paradigm. When added in combination with paroxetine, both isamoltane and GR 127935 significantly potentiated the effect of paroxetine on stimulated 5-HT efflux: isamoltane to 302 +/- 48% at maximum (p < 0.05 vs. paroxetine alone), GR 127935 to 318 +/- 95% (p < 0.05 vs. paroxetine alone) of pre-drug values. Neither isamoltane nor GR 127935 had any effect on 5-HT uptake. The selective 5-HT 1A antagonist WAY 100635 (10 nM) had no effect on 5-HT efflux or uptake, alone or in combination with paroxetine. These data suggest that, under these experimental conditions, paroxetine gives rise to tonic activation of the vLGN terminal 5-HT autoreceptors. Furthermore, these data show that 5-HT 1B and possibly 5-HT 1D antagonists block this inhibitory autoreceptor tone and may thus be a useful addition to SSRI treatment in the clinic.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9241443&dopt=Abstract paroxetine, Paxil, Paxil CR