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Interaction of tricyclic drug analogs with synaptic plasma membranes: structure-mechanism relationships in inhibition of neuronal Na+/K(+)-ATPase activity.

Perturbations of rat brain synaptic plasma membrane (SPM) bilayer structure and Na+/K(+)-ATPase activity were correlated for drugs that are structurally related and exhibit similar toxicological side effects but belong to different pharmacological classes. Na+/K(+)-ATPase IC50 values decrease linearly with increasing octanol/water partition coefficients (log-log plot) for a series of dimethylethylamine-containing drugs (i.e., chlorpromazine, amitriptyline, imipramine, doxepin, and diphenhydramine), emphasizing hydrophobicity in inhibition. However, nortriptyline and desipramine are 1.2 log uni…

Social stress induces neurovascular pathology promoting depression.

Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood-brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient

Persistent chest pain and no obstructive coronary artery disease.

Patients with persistent chest pain and no obstructive coronary artery disease are often labeled as having noncardiac pain and not offered further cardiologic testing or treatment. Diagnostic uncertainty for persistent chest pain is associated with adverse quality of life, morbidity, and health care costs. Two underdiagnosed cardiac causes for persistent chest pain include microvascular coronary disease and abnormal cardiac nociception. Microvascular coronary disease is associated with an increased risk of adverse cardiovascular events such as myocardial infarction, congestive heart failure, a

Clinical issues in the long-term treatment of panic disorder.

Longitudinal studies in naturalistic settings have shed new light on the course and value of therapeutic interventions in panic disorder and agoraphobia. Patients, their families, and clinicians need additional information about the natural course of the disorders and the factors that predispose patients to sustained illness, recovery, and relapse during treatment and upon treatment discontinuation. Clinical experience and controlled studies confirm the efficacy of pharmacologic and cognitive-behavioral therapy (CBT). Newer antidepressants, especially the serotonin selective reuptake inhibitor

Antitumoral Effects of Tricyclic Antidepressants: Beyond Neuropathic Pain Treatment.

Growing evidence shows that nerves play an active role in cancer development and progression by altering crucial molecular pathways and cell functions. Conversely, the use of neurotropic drugs, such as tricyclic antidepressants (TCAs), may modulate these molecular signals with a therapeutic purpose based on a direct antitumoral effect and beyond the TCA use to treat neuropathic pain in oncology patients. In this review, we discuss the TCAs' safety and their central effects against neuropathic pain in cancer, and the antitumoral effects of TCAs in in vitro and preclinical studies, as well as in

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… . | Partially reversion of the malignant phenotype. | [ 59 ] Imipramine blue followed by liposomal doxorubicin | Profilin-1, scinderin, α-actin, calgranulin, and RhoGDP dissociation inhibitor α. | Reduction in actin fiber Formation. | [ 60 ] Imipramine + ticlopidine | Imipramine activates adenylate cyclase … Imipramine is able to reduce the phosphorylation of ERK and P-65 NF-κB, leading to inactivation of ERK/NF-κB signaling transduction [ 55 ]. Imipramine can also inhibit the actin-binding protein fascin. This inhibitory effect is mediated by direct binding of imipramine to fascin [ 71 ]. …

Respiratory variability in panic disorder.

Disordered breathing may play an important role in the pathophysiology of panic disorder. Several studies have now indicated that panic disorder patients have greater respiratory variability than normal controls. In this study, we examine baseline respiratory measures in four diagnostic groups to determine whether greater respiratory variability is specific to panic disorder and whether effective anti-panic treatment alters respiratory variability. Patients with panic disorder, major depression, or premenstrual dysphoric disorder, and normal control subjects underwent two respiratory exposures

Psychopharmacology in childhood disorders.

Although not explicitly stated elsewhere, it should be clear that medication alone is rarely a sufficient treatment for childhood disorders and should usually be prescribed in conjunction with psychosocial interventions within a biopsychosocial framework. Even when cause is assumed to be largely or wholly biologic, as in infantile autism, there are secondary psychosocial consequences in the child and family that medication does not address. Finally, in the context of careful diagnosis and formulation, the appropriate use of medication is an essential component of effective management.

Prospects for repurposing CNS drugs for cancer treatment.

Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drug

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… The list of potential drugs includes Imipramine, Phenothiazines, Trifluoperazine, Pimozide, and Valproate. Imipramine Has shown efficacy against cancer as shown in several studies. Glioma A study was conducted both in vitro and in vivo to show the efficacy of Imipramine on glioma. … In vivo , a combination of Imipramine and Doxorubicin showed enhanced anti-invasive effect. 29 Whereas a combination of Imipramine and Ticlopidine exhibited a suppressing effect on the ATG7, a member of the autophagy survival signaling, resulting in cell death. 30 Breast Cancer Another reported use …