• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.88-97
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• 1994

Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.

• Sleep Medicine and Psychophysiology
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• v.1 no.2
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• pp.182-187
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• 1994

The Authors report a case of sleep paralysis patient who is 25-years old man. He complained that he has been experiencing episode "being suffocated" during sleep and could not move by himself while semiconsciousness state. He was a only son of divorced parents and could not attach anybody from yong childhood. His symptoms was began intermittently after his early teens. Medical history and physical examination revealed no significant finding. A nocturnal polysomnogram showed loss of muscle tone during terminal REM period and sudden hyperventilation attack followed by wake-up. Psychosocial stress and insufficient sleep were presumed to be an etiological factors. Imipramine 50mg per day almost completely relieved symptoms.

• The Korean Journal of Pain
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• v.9 no.1
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• pp.244-247
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• 1996

A 67 year old male with postherpetic neuralgia complained of right anterior chest throbbing pain and also allodynia. We performed thoracic epidural block with 0.25% bupivacaine and 1% lidocaine. Oral carbamazepine and imipramine were also administred concomitantly. One month later, patient complained of fatigue, anorexia, pruritis, jaundice, and dark urine. Liver function test values were significantly elevated then. Therefore we removed the epidural catheter and ceased all medication. Liver function test values decreased rapidly after discontinuation of medication. Hepatitis might have developed as result of drugs administered and could have been prevented if the patient had been monitored with regular clinical laboratory follow up. The purpose of this case report is emphasize the importance of early regular laboratory test to detect any possible side effect that may occur by administration of drugs during treatment of chronic pain.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.195-195
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• 2001

The inhibitory potentials of TCAs (imipramine, desipramine, amitriptyline, and nortriptyline) on phenytoin p-hydroxylation and probe metabolic pathways of each CYP isoforms were evaluated from incubation studies of human liver microsomes and cDNA-expressed cytochrome P450s in vitro in order to understand the mechanism of drug interaction between TCAs and phenytoin, a substrate of CYP2C9 and CYP2C19. (omitted)

• Journal of Oral Medicine and Pain
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• v.43 no.3
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• pp.92-96
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• 2018

A 39-year-old male presented with severe pain in right posterior mandibular teeth and temporal area. Initially, the pain in the mandibular teeth was moderate, but the concomitant headache was unbearably severe. His medical history was non-contributory. The clinical and radiographic examination failed to reveal any pathology in the region. There was no tenderness to palpation in the temporalis and masseter muscles or temporomandibular joints. The clinical impression was migraine. The pain in the teeth and headache were aborted using ergotamine tartrate and sumatriptan succinate. Atenolol prevented further pain, while amitriptyline and imipramine had no effect. Migraine can present as non-odontogenic pain in the mandibular teeth, although not as frequently as in the maxillary teeth. A correct diagnosis is essential to avoid unnecessary dental treatments and to manage pain effectively. Clinicians should be able to identify migraine with non-odontogenic dental pain and establish a proper diagnosis through a comprehensive evaluation.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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• pp.74-80
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• 1999

This study was performed to investigate the mechanism of the clozapine-induced seizures in partially restrained rats by concomitant treatment with drugs affecting monoaminergic systems. Partially restrained rats treated with acute single doses of 10mg/kg clozapine exhibited myoclonic jerks (MJs). Drugs affecting the monoaminergic systems, including 2mg/kg haloperidol, 5mg/kg propranolol, 2mg/kg ritanserin, 20mg/kg fluoxetine, and 20mg/kg imipramine, were concomitantly treated with clozapine to observe the effects of these drugs on the MJs. The drugs were given intraperitoneally either as acute single doses(haloperidol, propranolol, ritanserin, and fluoxetine) or as chronic doses for 21days(haloperidol, imipramine, ritanserin, and fluoxetine). The effects of the concomitant treatment of other drugs on the clozapine-induced MJs were evaluated by comparison of the total numbers of the MJs between the clozapine-treated and concomitantly treated groups. The results were as follows. 1) Concomitant treatment with acute single doses of haloperidol, propranolol, and fluoxetine reduced the total numbers of the clozapine-induced MJs, while concomitant treatment with ritanserin did not. 2) Concomitant treatment with chronic doses of imipramine and ritanserin increased the total numbers of the MJs, while concomitant treatment with fluoxetine reduced them. Concomitant chronic treatment with haloperidol did not affect the numbers of the MJs. These results suggest that dopamine and serotonin, not noradrenalin may be involved in the clozapine-induced MJs in partially restrained rats. Future research needs to study the function of each subtype of monoaminergic receptors on the mechanism of the clozapine-induced seizure.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.95-100
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• 1987

The effects of various drugs on muricide and hyperirritability induced by bilateral lesions of the nucleus accumbens septi (NAB) were investigated in comparison with those on aggression induced by midbrain raphe nuclei-lesioned rats (raphe) and olfactory bulbectomized rats (OB). Muricide in NAB, raphe and OB rats were markedly suppressed by atropine. Muricide in NAB and raphe rats were significantly suppressed by L-DOPA, L-5-HTP, but muricide in OB rats was scarcely suppressed by L-DOPA and L-5-HTP. Hyperirritability in NAB, raphe and OB rats were significantly reduced by L-DOPA and haloperidol but not suppressed by atropine. On the other hand, muricide in NAB rats was markedly suppressed by antidepressants, particularily, nomifensine, clomipramine and desipramine. Muricide in raphe rats was markedly inhibited by nomifensine and clomipramine but only slightly inhibited by desipramine. Muricide in OB rats was markedly suppressed by imipramine. Hyperirritability in NAB, raphe and OB rats were slightly suppressed by antidepressants. These results suggested that the pharmacological characteristics of aggression induced by NAB rats resembles that induced by raphe rats, but differs from that induced by OB rats. It is also suggested that employment of different types of experimentally induced muricide in rats can be useful for the evaluation of antidepressants.

• The Korean Journal of Pharmacology
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• v.21 no.2
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• pp.90-98
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• 1985

1) In the study of the forced-swimming test in mice (FSM), the duration of immobility posture was dose-dependently shortened by ${\alpha}_2$-agonists, clonidine and guanabenz. BH-T 933 and oxymetazoline also decreased it . Xylazine rather increased the immobility duration at low dose. 2) ${\alpha}_1$-Agonists, cirazoline, amidephrine and methoxamine, however, showed inconsistent effect on the immobility duration (ID). 3) The decrease in ID by clonidine and guanabenz was antagonized by pretreatment with yohimbine, idazoxan and phentolamine (${\alpha}_2$antagonist), but not by prazosin and corynanthine (${\alpha}_1$-antagonist) .4) The ID in the FSM was shortened dose-dependently by d-amphetamine, and it was also antagonized by yohimbine, but not by prazosin. 5) In the mice pretreated with either ${\alpha}$-methyl-p-tyrosine or reserpine, or with combination of both, the decrease in ID was still evoked by clonidine. 6) When the mice were chronically treated with antidepressants (desipramine and imipramine), or with electroconvulsive shock, clonidine still decreased the ID as it did in the control. 7) These results provided the evidences to hypothesize that the change of the ID in the FSM is closely related with the postsynaptie ${\alpha}_2$-adrenoceptor located on the central noradrenergic neuron body. Furthermore, it is assumed that this escape-directed behavior enhanced by ${\alpha}_2$-adrenoceptor agonist may be the result in some analogy with the incentive of drives which are directed toward the self-preservation.

• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.35-47
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• 1984

Contents of immunoreactive ${\beta}-endorphin$ and maximum of $^3H-morphine$ binding was measured in the rat midbrain homogenates from different subgroups at 24 hour interval over 24 hours. Animals were adapted to the light-dark cycle(L : D, 12: 12) or constant darkness (D : D, 12 : 12) for 3 weeks. After the adaptation, 0.5ml of physiologic saline or drug was administered twice a day for 2 weeks. A highly significant circadian rhythm with the peak$(94.8{\pm}7.7\;fmole/mg\;protein)$ at 06:00 and the nadir $(27.6{\pm}2.4\;fmole/mg\;protein)$ at 18:00 was observed in constant of group. Constant dark or treatment of reserpine, pargyline, imipramine, amphetamine and chlorpromazine modified the diurnal rhythm in the time of peak and nadir, shape, phase amplitude and 24 hour mean of ${\beta}-endorphin$ contents. Opiate receptor binding by $^3H-morphine$ also showed highly significant diurnal change in control and constant dark adapted rats. Statistical analysis by one-way analysis of variance and two-way analysis of variance indicates that the·re are highly significant differences between the diurnal change of ${\beta}-endorphin$ in control and those constant dark adapted and drug treated groups. However diurnal change of Maximum $^3H-morphine$ binding is closely related to the change of ${\beta}-endorphin$ contents. The results are interpreted with regard to the circadian rhythm of beta-endorphin contents, its modification by psychoactive drugs and possible mechanism of diurnal change of opiate receptor in brain.

• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.23-34
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• 1984

To investigate diurnal variations of opiate receptor binding and its modification by experimental condition or treatment of various centrally-acting drugs, the amount of maximum $^3H-morphine$ binding in rat midbrain homogenates was measured at 4 hour intervals for 24 hours. Animals were conditioned under the controlled L : D, 12 : 12 cycle or D: D, 12 : 12 cycle, for 3 weeks and treated with 0.5 ml of physiological saline or drugs for 2 weeks. A highly significant diurnal rhythm with peak at 22 hour of early dark phase with an amplitude$(0.68{\pm}0.06\;pmole/mg\;protein)$ of +51.1% and nadir $(0.33{\pm}0.03\;mole/mg\;prtein)$ at 18 hour of late light phase with an amplitude of -26.6% was found in control group. 24 tour mean of $^3H-morphine$ binding was $0.45{\pm}0.03\;pmole/mg$ protein respectively. Constant dark adaptation or treatment of reserpine, pargyline, imipramine, amphetamine and chlorpromazine modified the diurnal rhythm in the time of peak and nadir binding shape, phase, amplitude of the diurnal curve and 24 hour mean of $^3H-morphine$ binding. However, Kd values were not changed in all experimental groups : Statistical analysis at times of least and great binding indicates that the differences in $^3H-morphine$ binding were due to changes not in the affinity, but in the number of binding sites. The results are interpreted with regard to the diurnal rhythm of opiate receptor finding. The modes of action of psychoactive drugs are closely related to postulated changes of receptor sensitivity in neuropharmacological aspects.