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Extravascular use of drug-eluting beads: a promising approach in compartment-based tumor therapy.


Controversy exists regarding the relationship between anxiety states and major depression. We studied the binding of tritiated imipramine to platelet membranes in order to determine if patients with agoraphobia and panic attacks differed from depressed subjects or healthy volunteers on this biological parameter. Mean (+/- SD) Bmax and Kd values were significantly lower in patients with agoraphobia and panic attacks (787 +/- 276 fmole/mg protein and 0.35 +/- 0.14 nM, respectively) than in healthy volunteers (1237 +/- 201 fmole/mg protein and 0.71 +/- 0.37 nM, respectively). In addition, patients with agoraphobia and panic attacks had binding parameters that were similar to those of patients with bipolar or familial pure depressive disorder, but significantly lower than those of patients with depressive spectrum or sporadic depressive disorder. These findings have implications for both the nosology and pathophysiology of anxiety disorders.

In a 6-week double-blind trial 129 outpatients with major depressive disorder received either alprazolam, imipramine or placebo. Dosage was adjustable from 0.5 mg alprazolam, 25 mg imipramine or two capsules placebo b.i.d. to 4.5 mg alprazolam, 225 mg imipramine or three capsules placebo t.i.d. Both active drugs were more effective than placebo according to all the rating scales used. Alprazolam and imipramine did not differ consistently except in the somatic symptom cluster on the Hamilton Anxiety Rating Scale. Mean final daily dosage was 2.7 mg alprazolam, 117.3 mg imipramine and 7.2 capsules placebo. Patients on alprazolam reported fewer side effects than patients on imipramine and approximately the same number as patients on placebo. Anticholinergic side effects were commonly associated with imipramine; drowsiness was the most frequent side effect with alprazolam.

In confirmation of previous studies, the tricyclic agent imipramine (10.0 mg/kg) and the "atypical" agent mianserin (40.0 mg/kg) significantly increased efficiency. In analogy, the selective NE reuptake inhibitors (NARIs) desipramine (20.0 mg/kg), nortriptyline (2.5 mg/kg) and reboxetine (0.63 mg/kg) all displayed marked enhancements in efficiency. In contrast, the selective 5-HT reuptake inhibitors (SSRIs) citalopram (10.0 mg/kg), fluvoxamine (10.0 mg/kg) and paroxetine (10.0 mg/kg) all significantly decreased efficiency. The mixed 5-HT/NE reuptake inhibitors (SNRIs) venlafaxine (2.5 mg/kg, 10.0 mg/kg) and S33005 (0.16-10.0 mg/kg), likewise, did not increase efficiency. Further, the DA reuptake inhibitors (DARIs) bupropion (0.16-10.0 mg/kg) and GBR12935 (0.63-10.0 mg/kg) had no effect on DRL 72-s performance. All drug classes exerted a similar, mild inhibitory influence on food intake and locomotor behaviour. Imipramine, mianserin and NARIs markedly increased extracellular levels of NE, and SSRIs elevated levels of 5-HT, while SSRIs augmented levels of both.

To obtain information on the use of psychotropic drugs children outside the U.S.A., 251 questionnaires were mailed to institutions in 53 countries. Seventy-three responses from 34 countries were analyzed. The percentage of patients receiving drugs under the care of these respondents ranged from 0 to 100% (mean 39%). A total of 56 different drugs were selected for eleven psychiatric disorders. No regional differences were apparent, except for infrequently used drugs. Respondents differed widely in the number of drugs selected and maximum dosages. The most popular drugs used in most disorders were diazepam, thioridazine, chlorpromazine, chlordiazepoxide, imipramine, amitriptyline, haloperidol and methylphenidate. Highest agreements among respondents were for imipramine in enuresis, diazepam in anxiety, chlorpromazine in psychosis and thioridazine in hyperkinesis. The results of this survey illustrate important problems in interpreting cross-cultural data in pediatric psychopharmacology, and recommendations for future research are made.

Using the forced swimming test in mice, we examined the effect of the following antidepressants: citalopram, imipramine, desipramine and moclobemide (which are characterized by different mechanisms of action), administered in combination with the selective 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]-pyrrolidine (SB 269970). All those drugs were given in doses which did not shorten the immobility time of mice. Citalopram (1.25 mg/kg), imipramine (10 mg/kg), desipramine (5 mg/kg) or moclobemide (10 mg/kg) administered jointly with SB 269970 (5 mg/kg), produced a significant antidepressant-like effect. None of the compounds studied, given alone or in combination, increased the spontaneous locomotor activity of mice. The obtained results indicate that blockade of 5-HT7 receptors may facilitate the anti-immobility effect of antidepressants in mice.

5-Hydroxytryptamine (5-HT) reuptake inhibitors of the zimeldine-type have induced polyneuropathies similar to Guillain-Barré syndrome (GBS) in patients with endogenous depression. Some monoamine neurotransmitters have been shown to affect immune reactions in vivo and in vitro in a concentration-dependent manner. We therefore studied the effect of the monoamine reuptake inhibitory anti-depressants, clomipramine and imipramine on specific immune response and the clinical course of experimental autoimmune neuritis (EAN), the animal model of GBS in humans. Clomipramine and imipramine both suppressed clinical signs of EAN induced by immunization with bovine peripheral nerve myelin (BPM), when given at a dose of 20 mg/kg/day intraperitoneally, via osmotic pumps. Clomipramine and imipramine reduced the numbers of Th1 cells secreting IFN-gamma in response to the neuritogenic myelin proteins BPM, P0 and P2 among lymph node mononuclear cells (MNC) from rats with EAN. The levels of cells secreting IgG antibodies to BPM, P2 and GM1 in lymph nodes were reduced at the height of EAN in clomipramine and imipramine treated animals. The action of clomipramine and imipramine on induced IFN-gamma and anti-myelin antibodies suggests that the mechanism for the suppressive effect of those substances on EAN symptoms may be due to an action on myelin T and B cell autoreactivity. Considering that the main common pharmacological principle of clomipramine and imipramine is to increase the functional activity of the nor-adrenaline (NA) and serotonin (5-HT) of the monoamines, it seems justified to postulate that the actions of clomipramine and imipramine demonstrated in this study to some extent involve NA and/or 5-HT. The immunomodulatory effects of clomipramine and imipramine call for further research on the potential role of drugs acting on the monoamine system in the treatment of autoimmune diseases, and for further studies of immunological mechanisms in the pathogenesis of depressive disorders.