Chronic administration of imipramine decreases freezing time in rats genetically predisposed to catalepsy

The effects of acute and chronic imipramine treatment on the degree of catalepsy were compared in GC rats genetically predisposed to catalepsy. We recorded the time over which the rats remained in a vertical position they were placed. As differentiated from acute treatment, chronic administration of imipramine dose-dependently decreased the time of freezing in GC rats.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 10, pp. 450–453, October, 2004     

A Double-Blind Comparison of Sertraline and Imipramine in Outpatients with Major Depression: Acute (8 Weeks) and Continuation (16 Weeks) Treatment

In a double-blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared to those of imipramine, during an 8-week acute treatment phase followed by a 16-week continuation treatment phase in treatment responders. A total of 104 patients who met DSM-III-R criteria for major depression, HAM-D 17-item≥18 and Raskin Depression score>Covi Anxiety score, were randomized to receive either sertraline or imipramine. The initial daily dosage of 50 mg of sertraline or imipramine was rapidly titrated upwards in increments of 50 mg/day at weekly intervals, tolerability permitting, to a maximum of 200 mg/day by the fourth week. Eighty-eight patients completed at least 3 weeks of treatment and were included in the efficacy evaluable population. Both treatment groups demonstrated similar improvements on depression and anxiety rating scales during acute treatment, however, sertraline demonstrated significantly more improvement relative to imipramine on the HAM-D and Covi Anxiety scales after 1 week of treatment. Sertraline was more effective (HAM-D 17-item, CGI-S, SCL-56 Total score, SCL-56 Depression score, Covi Anxiety score) than imipramine in reducing depressive symptoms at the end of 24 weeks of treatment. There were significant improvements in all rating scales at week 24 relative to week 8 in the sertraline group but not in the imipramine group. The SCL-56 Total score, SCL-56 Depression score, Raskin Depression score and Covi Anxiety score at week 24 relative to week 8 showed significantly greater improvement in the sertraline group compared to the imipramine group. Imipramine was associated with a significantly higher incidence of dry mouth, sweating, constipation, palpitations, and a significantly higher heart rate and blood pressure. Sertraline was associated with a significantly higher incidence of diarrhoea/loose stools and insomnia. This study demonstrated a faster onset of therapeutic effect for sertraline relative to imipramine, reflecting the initiation of sertraline in a therapeutic dose of 50 mg/day and the need for gradual titration of imipramine to a therapeutic dose, at the beginning of treatment. Although efficacy was similar in both treatment groups at the end of the 8 weeks of acute therapy, sertraline-treated patients continued to manifest gradual improvements in depressive and anxiety symptoms during the 16 weeks of continuation therapy such that sertraline-treated patients were significantly more improved at the end of 24 weeks of therapy. © 1997 John Wiley & Sons, Ltd.     

Reboxetine,a selective noradrenaline reuptake inhibitor,is non-sedative and does not impair psychomotor performance in healthy subjects

A double-blind, randomized, four-way crossover study was performed to assess the CNS effects of reboxetine, a unique selective noradrenaline reuptake inhibitor (NRI). Eighteen volunteers received reboxetine (1 or 3 mg), imipramine (75 mg) or placebo at weekly intervals. Pharmaco-electroencephalography was recorded under high- and low-vigilance conditions and spectral difference index, total power and alpha slow-wave index (ASI) were calculated. In addition, skilled performance on psychometric tests and well-being were assessed. Absolute and relative power were relatively unaffected by reboxetine but increased by imipramine. Total power and ASI were unaffected or slightly increased by reboxetine, but reduced by imipramine. Reboxetine and imipramine decreased fronto-central θ and fast β power. In pharmaco-electroencephalography, imipramine showed a left shift in the occipito-temporal lead, with an increase in δ and θ and a decrease in α power. Reboxetine increased α power. Following reboxetine administration, the results in performance tests either did not differ from placebo or were better (Pegboard test). After imipramine, a deterioration in the Steadiness and Pauli test occurred. Critical flicker fusion and Vienna test results were unaltered by either drug. In summary, reboxetine, unlike the tricyclic antidepressant imipramine, has no sedative effects of electroencephalography or on any behavioural variable indicative of a decline in vigilance. Furthermore, reboxetine showed a vigilance-enhancing effect. © 1998 John Wiley & Sons, Ltd.     

Pharmacokinetic and pharmacodynamic study of suriclone imipramine interaction in man

Summary— Suriclone is a novel cyclopyrrolone exhibiting anxiolytic activity. Twelve healthy Causasian male volunteers participated in the study. A single dose of suriclone 0.4 mg, imipramine 75 mg, suriclone 0.4 mg + imipramine 75 mg, or placebo was given according to a 4 × 4 Latin-square design in order to assess the effect of drug association on pharmacokinetics and psychomotor performances. Visual analogue scale ratings, critical flicker frequency, choice visual reaction time, and Pauli, picture memory and Sternberg tests were performed before and 1.5, 6 and 9 h after drug administration. Suriclone, with the exception of the Pauli test, had no effect on psychomotor performances. The imipramine-suriclone association appeared to disturb some performances (no statistical significance), probably due to the effect of imipramine. Blood samples were collected for determination of imipramine and suriclone plasma levels respectively by high-performance liquid chromatography and radioimmunoassays. Suriclone AUC, C_max and T_max were not affected by imipramine, and reciprocally.     

Sodium lactate reversal of electrophysiological effects of imipramine in guinea-pig ventricular myocardium

Overdose cardiac effects of imipramine are due to fast Na channel blockade and are clinically reversed by administration of sodium lactate which induces alkalosis (about pH 7.50) and hypernatremia (about 8 mM). The mechanisms of this beneficial effect of Na lactate were explored in vitro on guinea-pig ventricular myocardium using the microelectrode technique. The time-course effects of the clinically relevant concentration of 10 microM imipramine on action potential characteristics were examined at pH 7.20 and pH 7.50. To test whether alkalinisation per se is important or whether an increase in Na concentration plays a major role in the reversal effect, preparations were exposed to increasing concentrations (1, 3, 10, 30, 100 mM) of either Na lactate, bicarbonate or chloride in the absence or in the presence of 10 microM imipramine at pH 7.50. The influence of elevating osmolality was evaluated with equivalent concentrations of sucrose. Imipramine alone significantly depressed Vmax and shortened action potential duration at all phases of repolarisation. All three high sodium solutions reversed imipramine effects. However the reversal effect was already obvious with 10 mM Na lactate and 10 mM NaHCO3 but not 10 mM NaCl. Osmolality did not reverse the imipramine-induced Vmax depression. The results suggest that at the clinically relevant 10 mM concentration, sodium lactate and bicarbonate may displace imipramine from its receptor site on the Na channel by causing alkalosis at the membrane level without profoundly affecting the driving force of the Na current, whereas at the upper concentrations, the increase in Na ion concentrations is predominantly involved in the reversal of imipramine effects.     

Specific binding sites for bifemelane in the hippocampus of the guinea pig, relevant to its pharmacological actions

Bifemelane has an anti-amnesic effect, produces the translocation of protein kinase C in the hippocampal CA3 region but not in CA1 and enhances long-term potentiation in the mossy fibre-CA3 system but not in the Schaffer collateral-CA1 system. The present study examined the specific binding of [³H]bifemelane in membrane preparations of guinea pig hippocampus and regional differences in such a binding. The binding of [³H]bifemelane was reversible and greater when incubated at 4°C than at 25 or 37°C. The binding of [³H]bifemelane appeared to be composed of at least 2 different affinity components. Imipramine significantly suppressed the binding of [³H]bifemelane at 1 μM and, in the presence of 1 μM imipramine, the low-affinity component of the binding of [³H]bifemelane was eliminated. The density of specific binding sites for 1 nM [³H]bifemelane was significantly higher in the hippocampal CA3 region than in the CA1. The specific binding of 1 nM [³H]bifemelane was not inhibited by other nootropic drugs, such as idebenone, calcium hopantenate, vinpocetine, indeloxazine and piracetam. The present results suggest that there are specific binding sites for bifemelane in hippocampus, which are different from those for other nootropic drugs tested and that the regional differences in the pharmacological susceptibilities to bifemelane are at least, in part, attributed to those in the density of binding sites for bifemelane.     

丙咪嗪抗血小板聚集作用与细胞外Ca_(2+)浓度的关系

目的：观察丙咪嗪抗血小板聚集作用与细胞外Ｃａ２＋浓度的关系。方法：以比浊度法进行血小板聚集实验。结果：丙咪嗪００１～１ｍｍｏｌ／Ｌ浓度明显对抗凝血酶及二磷酸腺苷诱导的人血小板聚集，且其抗血小板聚集作用随着细胞外Ｃａ２＋增加（加入ＣａＣｌ２１ｍｍｏｌ／Ｌ）与降低（加入乙二醇二乙醚二氨四乙酸１ｍｍｏｌ／Ｌ）而呈现减弱和增强现象，与维拉帕米作用相似。结论：丙咪嗪的抗血小板聚集作用可能与抗钙作用有关。     

Comparison of imipramine-imipraminium in mice. To elucidate central or peripheral origin of effects of imipramine

Imipramine hydrochloride shows effects in a battery of tests used for the screening of antidepressant drugs. The central origin of these pharmacological effects of imipramine has not been clearly established. Imipramine methiodide is a quaternary derivative of imipramine which does not cross the blood-brain barrier easily. The effects of the two forms of imipramine have been compared: on an effect known to have a central origin; on two effects known to have a peripheral origin; on a battery of tests used for the screening of antidepressant drugs. It has been demonstrated that imipramine methiodide is as active as imipramine hydrochloride on two effects of peripheral origin, less active than imipramine hydrochloride on an effect considered to have a central origin and less active than imipramine hydrochloride or inactive on the tests which are used for the screening of antidepressant drugs. Consequently, the tests used for the screening of antidepressant drugs represent, primarily or exclusively, effects of central origin.     

西酞普兰治疗老年抑郁症的对照研究

目的:比较西酞普兰与丙米嗪治疗老年抑郁症的疗效及安全性。方法:将72例老年抑郁症患者随机分成两组。其中,研究组36例,应用西酞普兰治疗;对照组36例,应用丙米嗪治疗;疗程均为6周。采用汉密尔顿抑郁量表,临床疗效总评定量表评定临床疗效,副反应量表、评定药物的不良反应。结果:两组总体疗效相当(P>0.05),但西酞普兰组不良反应较丙米嗪组发生率低。结论:西酞普兰治疗老年抑郁症疗效显著,不良反应少,安全性高。