Injection Of Desmethylimipramine Research Articles

The influence of desmethylimipramine on the hypothalamic and neurohypophysial vasopressin content in pinealectomized male rats.

The effect of desmethylimipramine (DMI) on the hypothalamic and neurohypophysial vasopressin content was investigated in normal and pinealectomized male rats. The vasopressor activity of the hypothalamus and neurohypophysis was bioassayed by the method of Dekański (1952). A single i.c.v. injection of DMI (20 micrograms; dissolved in 10 microliters of normal saline) decreased vasopressin content in the neurohypophysis of non-operated and sham-operated animals. In pinealectomized rats the vasopressin content in the neurohypophysis diminished and was not modified by an i.c.v. DMI injection. Repeated treatment with DMI (i.p.; 10 mg/kg, twice a day over five days) resulted in a distinct increase of the hypothalamic and neurohypophysial vasopressin in both normal and pinealectomized rats.

Effects of concurrent subchronic treatments with desmethylimipramine and propranolol on beta-adrenergic and serotonin2 receptors in rat brain

The effects of seven consecutive daily injections of desmethylimipramine (DMI 20 mg/kg) and propranolol (PRO 10 mg/kg) on 3H-dihydroalprenolol (3H-DHA) and 3H-ketanserin (3H-KET) binding in rat brain were examined. Analyses of saturation binding data using the iterative, nonlinear curve-fitting program LIGAND revealed that PRO increased, while DMI reduced, 3H-DHA binding site density in cerebral cortex without altering receptor affinity, as previously reported. DMI reduced 3H-KET binding site density without changing affinity, and PRO produced the same effect. In cerebral cortex and probably in hippocampus and striatum, DMI and PRO administered together increased the density of 3H-DHA binding sites (beta-adrenergic receptors) and reduced their affinity. This combination of drugs reduced the density of 3H-KET binding sites (5-HT2 receptors) in cerebral cortex, but did not change their affinity. These findings indicate a need for additional studies on the interactions of DMI and PRO and related drugs because of implications for the treatment of depressed patients with cardiovascular disorders.

In mice repeated administration of electroconvulsive shock or desmethylimipramine produces rapid alterations in 5-HT 2-mediated head-twitch responses and cortical 5-HT 2 receptor number

Mice treated with a single electroconvulsive shock (ECS) daily for up to 3 days showed progressively enhanced head-twitch to 5-methoxy-N,N'-dimethyltryptamine 24 h after 1, 2 and 3 shocks. Injection of desmethylimipramine (DMI, 5 mg/kg) twice daily for up to 3.5 days progressively decreased head-twitch responses on days 2, 3 and 4. Cortical [ 3H]ketanserin binding was increased by ECS × 3 and decreased by 3.5 days DMI treatment. These data demonstrate that in mice antidepressant treatments produce rapid changes in central 5-HT 2 function.

Interaction between thyroxine and tricyclic antidepressant drugs on cardiac neurotransmitter receptors.

The effect of chronic administration of desmethylimipramine (DMI) and iprindole on cardiac neurotransmitter receptors was studied. In addition, the influence of these drugs on the action of thyroxine (T4) on myocardial receptors was investigated. Administration of iprindole (10 mg/kg i.p., twice daily for 11 days) markedly increased the number of beta- adrenergic receptors in the heart and significantly reduced the affinity of these receptors for (-)[3H]dihydroalprenolol ([3H]DHA). Injection of T4 (500 mg/rat i.m., for 5 days) concomitantly with iprindole resulted in a lower beta-adrenergic receptor density that with iprindole treatment alone, but significantly higher than that measured in control rats. Affinity of the receptors for (-)[3H]quinuclidinyl benzilate ([3H]QNB) in heart membrane preparations of animals pretreated with T4 alone or with T4 plus iprindole was not different from control. Neither pretreatment with DMI nor with iprindole affected the density of cholinergic muscarinic receptors in the heart or their affinity for [3H]QNB. The decrease in cardiac cholinergic receptors induced by administration of T4 was not prevented by simultaneous injections of DMI. Combined administration of iprindole and T4 caused a reduction in the affinity of myocardial cholinergic muscarinic receptors, but restored the number of these receptors to normal. The results demonstrate distinct differences between DMI and iprindole in their effects on cardiac neurotransmitter receptors and in the influence of these drugs on the actions of T4 on receptors in the heart.

Opposite effects of acute and repeated administration of desmethylimipramine on adrenergic responsiveness in rat pineal gland

The effect of acute and repeated desmethylimipramine (DMI) treatment on catecholamine-stimulated production of adenosine 3', 5'-monophosphate (cyclic AMP) in rat pineal gland was studied in vivo . In rats exposed to continuous illumination, the administration of isoproterenol (2μmol/kg) to control animals produced a marked increase in the concentration of cyclic AMP in pineal gland. In contrast, norepinephrine (2μmol/kg) failed to increase the levels of cyclic AMP. After acute treatment with DMI (single injection, 38μmol/kg, i. p.), the isoproterenol-induced rise in cyclic AMP was not significantly different from that measured in control animals. However, acute DMI treatment did allow a significant elevation in the concentration of cyclic AMP in pineal gland in response to norepinephrine. In rats given nine injections of DMI (38μmol/kg, i.p., twice daily) neither isoproterenol nor norepinephrine caused a significant increase in the concentration of cyclic AMP in pineal glands. Although acute treatment with DMI had no significant effect on [ 3H] dihydroalprenolol binding, chronic treatment with DMI significantly reduced [ 3H] dihydroalprenolol binding in the pineal gland. The results of this study suggest that while a single administration of DMI can enhance adrenergic responses elicited by norepinephrine, chronic administration of DMI leads to compensatory decreases in receptor density and adrenergic responsiveness.

Effect of desmethylimipramine on the canine SA node.

Direct perfusion of the sinus node artery at constant pressure of 100 mmHg was performed in eleven canine hearts in situ. The injection of desmethylimipramine (DMI) into the sinus node artery caused an initial short deceleration followed by markedly long-lasting acceleration of the heart rate. The initial deceleration was not influenced by treatment with atropine. The secondary acceleration was inhibited by propranolol, and, furthermore, suppressed by tetrodotoxin. After the treatment with propranolol or tetrodotoxin, DMI produced only a negative chronotropic effect dose-relatedly. It was difficult to observe the blocking effect of DMI on tyramine action, because DMI alone induced marked sinus acceleration. On the other hand, tyramine action was not influenced by tetrodotoxin. Therefore, the use of both DMI and tetrodotoxin is beneficial to observe blocking effect of DMI on tyramine-like action in the in situ SA node preparation.

The effects of intrahypothalamic injections of desmethylimipramine on food and water intake o the rat.

The effects on eating and drinking of injections of desmethylimipramine (DMI) into the lateral hypothalamus of the rat were examined under four conditions of food- and water-deprivation (food- and water-satiated; 16 hr food-deprived and water-satiated; food-satiated and 11 hr water-deprived; 16 hr food-deprived and 11 hr water-deprived). DMI increased eating in animals that were food-deprived and water-satiated; and increased drinking in animals that were food- and water-satiated. No other effects on eating and drinking were observed. The results are discussed in terms of current hypotheses concerning the adrenergic and cholinergic actions of DMI and other tricyclic antidepressants.