• Molecules and Cells
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• v.38 no.8
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• pp.734-740
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• 2015

Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson' disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo. We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells. When injected into mice on a subchronic schedule, amitriptyline induced movement deficits in the pole test, which is known to detect nigrostriatal dysfunction. In addition, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was reduced in amitriptyline-injected mice. Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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• pp.34-40
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• 1999

New antidepressants have become available for clinical use in the 1990s. Before this decade, the drugs available to treat depression consisted essentially of monoamine oxidase inhibitors, tricyclic antidepressants, and lithium. Following the introduction of SSRIs, the options have expanded and now include SSRIs, nefazodone, venlafaxine, mirtazapine, reboxetine, tianeptine. Newer antidepressants possess a variety of pharmacological characteristics that are relevant to the choice of an antidepressant for clinical use. This review summarizes some of the major pharmacological characteristics among the drugs.

• Korean Journal of Biological Psychiatry
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• v.23 no.1
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• pp.1-11
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• 2016

Development of various antidepressants such as monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressant has led to a tremendous progression of pharmaceutical treatment for depression, but still there are some limitations of current antidepressants, such as treatment-resistant depression and delayed onset of antidepressants. The pathogenesis of depression is unclear because depression is a heterogeneous disease state, and the mechanisms of antidepressants remain uncertain as well. Nevertheless, in an attempt to develop novel antidepressants, some trials have been conducted based on the potential biological mechanism discovered in the numerous research results. This review will provide information about the potential novel antidepressants and the current states of clinical studies using them. In particular, some potential novel antidepressants anti-inflammatory agents, antioxidants, anticholinergics, modulators of Hypothalamic Pituitary Adrenal Axis, glutamate, and opioid systems, as well as some neuropeptides such as susbstance P, neuropeptide Y, and galanin will be discussed.

• Journal of Hospice and Palliative Care
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• v.1 no.1
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• pp.65-68
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• 1998

The neuropathic pains are not well controlled by common analgesics and opioid drugs in terminal cancer patients. The types of these pains are divided within the two cages, one is due to continuous central sensitization and the other is due to paroxymal peripheral sensitization. The mechanism of continuous central sensitization is the activity of dorsal horn neurones that are activated by C-fiber input. The tricyclic antidepressants, non-tricyclic antidepressants, and oral local anaesthesia probably produce analgesic effects in neuropathic pains through suppression of this activity. The mechanism of paroxymal peripheral sensitization is the hyper-excitability of peripheral neurones. The neuropathic pains due to peripheral sensitization respond relatively the anticonvulsants and baclofen that stabilize membranes and suppress paroxymal electrical discharge. The patients was a 38-year-old female who complained of hyperthemia on upper right extremity. The symptom of this patient was improved with anticonvulsant(dilantin 600mg).

• YAKHAK HOEJI
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• v.55 no.2
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• pp.98-105
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• 2011

To search the minimum structural requirement of tricyclic isoxazole analogues (1~30) as new class potent antidepressant, thee-dimensional quanti- tative-structure relationship (3D-QSAR) models between substituents ($R_1{\sim}R_5$) of tricyclic isoxazoles and their antidepressant activity against medetomidine-induced loss of righting were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indies analysis (CoMSIA) methods. The correlativity and predictability ($r^2$=0.484 and $q^2$=0.947) of CoMSIA-2 model were higher than those of the rest models. The inhibitory activity against medetomidine-induced loss of righting was dependent on electrostatic field (43.4%), hydrophobic field (35.3%), and steric field (21.2%) of tricyclic isoxazoles. From the CoMSIA-2 contour maps, it is predicted that the antidepressant activity of potent antidepressants against medetomidine-induced loss of righting will be able to increase by the substituents ($R_1{\sim}R_5$) which were in accord with CoMSIA field.

• Korean Journal of Biological Psychiatry
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• v.2 no.1
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• pp.20-27
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• 1995

Therapeutic montitoring of drugs is a well established clinical 1001. However, the state of art is somewhat less advanced for psychotrpoic agents than it is for other classes of drugs, for several reasons. Most psychotropics have large volumes of distribution and achieve relatively low plasma concentrations following therapeutic doses. Many have one or more active metabolites. As a consequene, the analytical methodologies are often complex and not always reliable; well-controlled clinical studies are difficult to perform; and therapeutic ranges have been difficult to establish. Despite these limitations, prudent and selective monitoring of serum drug concentrations, particularly of the tricyclic antidepressants can be helpful in clinical management. This paper presents an overview of clinical and mothodological issues surrounding the utility of blood level measurement.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.168-178
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• 1997

The serotonin has been known to play important roles in pathology of the mood disorders. We summerize the evidences of serotonin in pathology of the mood disroders in a view of neuroanatomical and neurochemical aspects. Nowaday, the selective serotonin reuptake inhibitors(SSRIs) may be practically the first line of antidepressants with traditional tricyclic antidepressants(TCAs). Authors review the role of serotonin in the treatment of the mood disorders, in a view of the general considerations in selecting antidepressants, pharmacology, therapeutic indications, side effects, doses of medication, drug-discontinuation syndrome, drug-to-drug interactions, and special therapeutic situations.

• The Korean Journal of Physiology
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• v.26 no.2
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• pp.137-141
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• 1992

The present study was aimed at elucidating the mode of inhibitory action of tricyclic antidepressants on the smooth muscle. Effects of amitriptyline on the isolated detrusor muscle strips of the urinary bladder of the rabbit were examined. The spontaneous rhythmic movement of the muscle preparation was frequently observed, which was decreased or abolished by addition of amitriptyline $(10^{-5}{\sim}10^{-3}\;M)$. The muscle preparation responded with contraction dose dependently to carbachol, of which dose response curve shifted to the right in the presence of either amitriptyline or atropine. However, amitriptyline produced a nonparallel shift, whereas atropine caused a parallel one. In calcium free medium, the contraction response to carbachol was markedly decreased, which was resumed by the addition of $CaCl_2$ (2.5mM), but not in the presence of either amitriptyline or nifedipine. KCI (60 mM) produced a potent contraction, which was abolished in the presence of amitriptyline or nifedipine. These results suggest that amitriptyline, unlike atropine, not only acts as a noncompetitive antagonist at cholinergic muscarine receptors but also inhibits Ca-influx through the muscle cell membrane.

• Korean Journal of Psychosomatic Medicine
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• v.7 no.2
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• pp.274-280
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• 1999

A variety of mechanism may generate pain resulting from injury to the central and peripheral nervous system. None of these mechanism is disease-specific, and several different pain mechanism may be simultaneously present in anyone patient, independent of diagnosis. Diagnosis of neuropathic pain is often easily made from information gathered on neurologic examination and from patient history. Although treatment of neuropathic pain may be difficult, optimum treatment can be achieved if the neurologist has a complete understanding of therapeutic options, the mainstay of which is pharmacotherapy. Selection of an appropriate rharmacologic agent is by trial and error since individual responses to different agents, doses, and serum levels are highly variable. An adequate trial for each agent tried is key to pharmacologic treatment of neuropathic pain. Tricyclic antidepressants are first-line agents, although other drugs, including anticonvulsants, local anesthetic antiarrhythmics, clonidine, opiates, and certain topical agents, also offer pain relief in some patient populations. The novel antidepressants venlafaxine and nefazodone are potentially useful new drugs that are better tolerated than tricyclic antidepressants. Also Gabapentine seems an interesting and promising drug for the treatment of neuropathic pain.

• Journal of The Korean Society of Clinical Toxicology
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• v.8 no.2
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• pp.97-105
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• 2010

Purpose: Although cardiac toxicity is a key parameter of significant toxicity, in antidepressant intoxication, there are few studies on the cardiac toxicity of serotonin reuptake inhibitor and the intoxication with the new generation of antidepressants. The aim of this study is to investigate the relative cardiac toxicity of serotonin reuptake inhibitor and intoxication with the new generation of antidepressants as compared with that of tricyclic antidepressant intoxication. Methods: We retrospectively reviewed the medical records of 109 antidepressant intoxicated patients who visited the Emergency Department from January, 2005 to December, 2009 to collect and analyze the demographic and clinical data. Sixteen patients were excluded. The enrolled seventy eight patients were classified into three groups: the tricyclic antidepressant group (TCA) (n=32), the selective serotonin reuptake inhibitor subgroup (SSRI) (n=28) and the new generation antidepressant subgroup (NGA) (n=18). Results: The demographic and clinical data of the SSRI and NGA groups were not significantly different from that of the TCA group. The QRS duration of the SSRI subgroup ($86.4{\pm}12.0$ msec) and the NGA subgroup ($91.8{\pm}11.9$ msec) was not significantly different from that of the TCA group ($90.0{\pm}13.5msec$) (p=0.598). The QTc interval of the SSRI group ($444.5{\pm}33.5msec$) and the NGA group ($434.9{\pm}35.9msec$) (p=0.260) were not significantly different from that of the TCA group ($431.2{\pm}44.1msec$) (p=0.287). Conclusion: Intoxication with SSRI and the new generation antidepressants seemed to show significant cardiac toxicity, like what is seen in tricyclic antidepressant intoxication. Clinicians must pay attention to SSRI and new generation antidepressant intoxication.