Neurophysiological evidence for tricyclic antidepressant-induced decreased beta-adrenergic responsiveness in the rat hippocampus

A study was made in rats of the effects of chronic treatment with the tricyclic antidepressant agent imipramine on the increase in the population spike amplitude produced by the beta-adrenergic receptor agonist isoproterenol in the ‘in vitro’ slice preparation of the hippocampus. A significant reduction of 39% and 44% of the population spike increase was observed at 5 × 10⁻⁷ M and 1 × 10⁻⁶ M isoproterenol respectively in rats treated for 28 days with 10 mg/kg i.p. imipramine.     

阿普唑仑与米帕明治疗抑郁性神经症的对照试验

报道阿普唑仑(男性16,女性14,年龄30.1±s 1.9a,剂量2.4mg±1.2mg/d,6wk)和米帕明(男性14,女性12,年龄28.2±1.7a,剂量175mg±25mg/d,6wk)治疗抑郁性神经症56例的对照试验。结果2组治疗前到结束HAMD,SDS总分降低差别显著(P<0.01),而药物显效时间、治疗总有效率2组差别不显著。TESS评分阿普唑仑的不良反应显著少于米帕明。     

The electrocardiographic and anticholinergic effects of trazodone and imipramine in man

Summary The electrocardiographic and anticholinergic effects of trazodone (150 mg) and imipramine (75 mg) were investigated in 8 healthy volunteers. Both agents increased the QTc interval and decreased T wave height, but the effects occurred earlier with trazodone (from 30 min onwards) than with imipramine (150 and 180 min after dosing). Both drugs decreased heart rate, imipramine at 30 and 60 min and trazodone at 90 min. After 120 min, heart rate began to increase with imipramine an effect which was not seen with trazodone. Salivary volume was significantly decreased by imipramine at 120 and 180 min whereas trazodone did not influence salivary volume. Plasma levels of trazodone and imipramine were significantly related to the decrease in T wave amplitude. The increase in QTc interval correlated significantly with the plasma level of imipramine. These results suggest that trazodone, like the tricyclic antidepressants prolongs ventricular repolarization; but, in contrast to imipramine, it does not have anticholinergic activity.     

Longitudinal course of panic disorder: clinical and biological considerations

The longitudinal course of panic disorder and its associated symptoms were investigated in thirty-eight patients. The temporal relationships among panic attacks, generalized anxiety, agoraphobia and depression are described. Similar and different biological alterations in the tricyclic-responsive disorders of primary depression and panic disorder are reviewed and discussed.     

Inhibition by Reserpine,Guanethidine and Imipramine of the Uptake of 5-Hydroxytryptamine by Rat Peritoneal Mast Cells in Vitro

The effect of reserpine, guanethidine and imipramine on the uptake of tritiated 5-hydroxytryptamine by rat peritoneal mast cells was studied in vitro. The K_m value for uptake of 5-hydroxytryptamine was 3 × 10^-7 M in this study. Kinetic analysis of the data obtained suggests that the drugs inhibit the uptake in a competitive manner, in the order of decreasing potency: reserpine, imipramine, guanethidine. For reserpine the Dixon plot resulted in two curves, each composed of 2 linear components suggesting inhibition of uptake of 5-hydroxytryptamine at 2 different levels or by 2 different mechanisms with different K₁ values. It is suggested that the higher K₁ value, representing an immediate effect of reserpine, stands for inhibition of uptake at the cell membrane. The lower K₁ value possibly represents inhibition at the level of the membranes surrounding the intracellular storage organelles.     

The detection of specific [H]imipramine binding in bovine retina

Using [³H]imipramine, specific imipramine binding was demonstrable in the crude membrane homogenate of bovine retina. Scatchard analysis of the saturation experiments revealed an apparent dissociation constant (K_d) of 6.4 nM and a maximal number of binding sites of 780 fmol/mg protein. These results and the substrate specificity show that the properties of imipramine binding to retinal membranes are essentially the same as described for the rat brain.     

Symptom reduction in depression after treatment with L-tryptophan or imipramine. Item analysis of Hamilton rating scale for depression.

Thirty-eight in-patients with endogenous- and 20 in-patients with non-endogenous depression, took part in a multi-centre 3-week double-blind trial where patients were randomly allocated to treatment with either 6 g L-tryptophan or 150 mg imipramine daily. Item analysis of Hamilton ratings, before the investigation and weekly during the trial period demonstrated few statistically different mean scores on individual items between the two treatment groups. After 3 weeks' treatment a statistically significant item mean reduction on the 0.1% level was found in the item Agitation in favour of imipramine-treated, and in the item Work and Activities in favour of L-tryptophan-treated endogenously depressed patients. After 3 weeks' treatment a statistically significant item mean reduction on the 5% level was found in the item Suicide in favour of imipramine-treated non-endogenously depressed patients. The present study has shown that, after 3 weeks' treatment, imipramine and L-tryptophan has decreased the mean score on individual items of HRS in about the same degree.     

Does 3H-imipramine binding asymmetry indicate psychiatric illness?

We have accepted that serotonin is essentially an inhibitory neurotransmitter in the human brain, so we propose that it is precisely this inhibiting effect that has weakened in psychiatric cases. We have investigated the asymmetry of tritiated imipramine binding sites (Bmax) in the frontal cortices of homicide victims (n = 6) and controls (n = 6) who died of natural causes. Of these homicide victims examined in our experiment, five proved to have been psychiatric cases and one case had no psychiatric record. The two groups were comparable in age, gender and postmortem delay. The number of imipramine binding sites (Bmax) in the frontal cortices of controls was significantly higher in the right hemisphere than in the left hemisphere. But the homicide victims who were psychiatric cases had significantly higher (Bmax) values in the left hemisphere. While we only found higher Bmax values in the left hemisphere of homicide victims with mental diseases, our data may serve to prove the direct role of the serotonergic mechanism in the development of psychiatric cases.     

Inhibition of serotonin uptake by synaptosomes and glial cells induced by certain drugs

Uptake of [¹⁴C]serotonin by glial cells and synaptosomes in the rabbit cerebral cortex was studied. The value of K_m for serotonin uptake was the same (0.083±0.02 M) for both synaptosomes and glial cells. Cortical synaptosomes took up serotonin twice as fast as glial cells (the rates of uptake were compared as protein). Of the psychotropic drugs tested, the most active inhibitors of both synaptosomal and glial serotonin uptake were the tricyclic antidepressant imipramine and the psychostimulant cocaine which, in concentrations of 50 M, inhibited uptake of [¹⁴C]serotonin in synaptosomes by 90% and in glial cells by 75–80%.Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Biochemistry, Tbilisi University. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 11, pp. 564–566, November, 1979.     

Effect of chronic administration of imipramine on 2A-serotonin receptor mRNA in brain cortex of rats predisposed and resistant to catalepsy

Rats selected by predisposition to catalepsy showed decreased level of 2A-serotonin receptor mRNA in the frontal cortex in comparison with Wistar rats (p<0.05). Chronic administration of tricyclic antidepressant imipramine hydrochloride 2-fold increased the content of receptor mRNA in genetically cataleptic rats (p<0.001) and did not change this parameter in Wistar rats. These results prompted us to revise current notion on the mechanisms of chronic effect of imipramine on 2A-serotonin receptors.