1.Influence of the brain noradrenergic system on the rotational behavior induced by apomorphine in the substantia nigra-lesioned rat.
Keun Young PARK ; Sang Eun YOO ; Hong Bai EUN
Journal of Korean Neuropsychiatric Association 1993;32(5):767-775
No abstract available.
Animals
;
Apomorphine*
;
Brain*
;
Rats*
2.Expression of Dopamine D2 Receptor in Response to Apomorphine Treatment in the Striatum of the Rat with Experimentally Induced Parkinsonism.
Seung Jin CHOI ; Jae Hoon SUNG ; Byung Chul SON ; Choon Keun PARK ; Sung Oh KWON ; Moon Chan KIM ; Sang Won LEE
Journal of Korean Neurosurgical Society 2000;29(7):868-876
No abstract available.
Animals
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Apomorphine*
;
Dopamine*
;
Parkinsonian Disorders*
;
Rats*
;
Receptors, Dopamine D2*
3.The infraspinal neural pathway of apomorphine-induced erection : an experimental study by the comparison with electrostimulation-induced erection on the rat model.
Sung Won LEE ; Jae Seung PAICK ; Kwan Hyun PARK ; Seung Joon OH ; Myung Soo CHOO ; Hyung Kee JO
Korean Journal of Urology 1993;34(5):790-795
The erectile response is peripherally mediated by cavernous nerve that contains thoracolubar sympathetic nerve and sacral parasympathetic nerve. It is known that thoracolubar sympathetic nerve involves in detumescence and sacral parasympathetic nerve in tumescence, however there are some opinions that rhoracolubar sympathetic nerve participates in psychogenic erectile mechanism. We previously reported that by the comparison with electrostimulation-induced erection, apomor- phine-induced erection was a vascular event. The aim of our study was to determine the infraspinal neural pathway of APO-induced erection. The sham operated rats remained normal in all measured respects. All rats having undergone neurotomy ot the hypogastric nerves showed APO-induced erection except one. The only 5 rats having undergone neurotomy of the pelvic nerves showed APO-induced erection. Erections could be elicited upon cavernous or pelvic nerves stimulation in all rats having undergone neurolomy of the hypogastric nerves. Among 17 rats having undergone neurotomy of the pelvic nerve erection could be elicited upon cavernous nerves slimulation in 14 rats, however. the intracavernous pressure (47.9+/-16.5 mmHg) was lower than that found in sham-operated rats. Erectile response in these 14 rats appeared to result from stimulation of penile neurons coming from the major pelvic ganglion. In contrast to no response in sham-operated rats, stimulation of the hypogastric nerves also resulted in erections in 7 out of 17 rats. In conclusion, this present study suggests that APO-induced ereclion is primarily mediated via the sacral parasympathetic nerve system and may be mediated by the thoracolumbar sympathetic pathway following injury to the parasympathetic nerve system. Furthermore we can guess the possibility that the neural pathway of psychogenic erection is same that of AP0- induced erection.
Animals
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Apomorphine
;
Ganglion Cysts
;
Models, Animal*
;
Neural Pathways*
;
Neurons
;
Rats*
4.Effects of Fetal Nondopaminergic Cortical Tissue Transplantation in the Rat Parkinsonian Model.
Jin Woo CHANG ; Sang Sup CHUNG
Journal of Korean Neurosurgical Society 1994;23(5):487-498
Fetal dopaminergic or nondopaminergic cortical tissues were implanted directly into the denervated striatum of partial lesioned rat parkinsonian models. After transplantation, at rats were behaviourally tested with apomorphine and sacrificed for tyrosine hydroxylase immunohistochemical stain. The results of this study are summarized as follows : 1) Of 45 rats partially lesioned with 6-hydroxydopamine, 17 rats(37.8%) met a criteria(a minimum of 4 times/min to apomorphine-induced rotation test) of the rat parkinsonian model. 2) Eight weeks after transplantation of the fetal dopaminergic tissues into the striatum of the rat parkinsonian model, transplanted dopaminergic cells were found to be alive. Also reinnervated dopaminergic fibers were found in the previously denervated striatum. And the behavioural study suggested that the transplantation of the fetal dopaminergic neurons had influenced on the apomorphine-induced rotation. 3) Eight weeks after transplantation of the fetal nondopaminergic tissues into the striatum of the rat parkinsonian model, dopaminergic cells were not found in the previously denervated striatum. However, reinnervation of the dopaminergic fibers were found in the preciously denervated striatum. However, reinnervation of the dopaminergic fibers were found in the previously denervated striatum as well as the reduction of the apomorphine-induced rotation compared to the pregraft state. The major finding of this study support a trophic hypothesis for the mechanism of recovery in response to fetal dopaminergic or nondopaminergic tissue. The author conclude that fetal nondopaminergic tissue also had some beneficial effect in reducing apomorphine-induced rotational asymmetry probably by promoting recovery or sprouting of remaining dopaminergic fibers at the previously denervated striatum of the rat parkinsonian model.
Animals
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Apomorphine
;
Dopaminergic Neurons
;
Oxidopamine
;
Rats*
;
Tissue Transplantation*
;
Transplantation
;
Transplants*
;
Tyrosine 3-Monooxygenase
5.The Significance of Apomorphine-Induced Rotational Behavior in Partial Lesioned Rat Parkinsonian Models with 6-hydroxydopamine.
Yong Gou PARK ; Hyung Shik SHIN ; Jin Woo CHANG ; Sang Sup CHUNG
Journal of Korean Neurosurgical Society 1996;25(3):483-492
An apomorphine-induced rotational test has been used in the evaluation of rat parkinsonian models lesioned with neurotoxin 6-hydroxydopamine (6-OHDA). Previous parkinsonian rat models have generally been characterized by unilateral destruction of both nigrosriatal pathway and mesolimbic pathway using 6-OHDA. The authors created partial lesioned rat parkinsonian models using 6-OHDA in which there is destruction of the dopaminergic nigrostriatal pathway and sparing of the mesolimbic pathway. Rats with unilateral lesions of the substantia nigra pars compacta(SNpc) were tested for rotational asymmetry using a cylindrical rotometer device with flat bottom(diameter, 30.5cm) after administration of apomorphine. After completion of the rotation test, the animals were sacrificed and their brains were immunolabeled for tyrosine hydroxylase(TH). Analysis of anatomical and behavioral data suggests that the pattern of rotation(pivotal rotation) is more reliable index for loss of TH-immunoreactive neurons in lesioned SNpc than the total number of rotational responses to apomorphine. The exact cause of the abnormal ipsiversive rotation which some rats showed is unclear. Further research should be pursued to explain this finding.
Animals
;
Apomorphine
;
Brain
;
Models, Animal
;
Neurons
;
Oxidopamine*
;
Parkinson Disease
;
Rats*
;
Substantia Nigra
;
Tyrosine
6.Effects of a New Antipsychotic Drug (YKP1447) on Impaired Prepulse Inhibition Induced by Apomorphine and Phencyclidine in Rats.
Byung Soo YOON ; Eun Hye PARK ; Eui Ho PARK ; Jeong Tae KWON ; Sung Bin HONG ; Seon Min DONG ; Yun Hee KIM ; Joon HEO ; Mi Kyung JI ; Yong Gil KIM ; Byong Sung KWAK ; June Seek CHOI ; Hyun Taek KIM
Korean Journal of Psychopharmacology 2008;19(1):38-45
OBJECTIVE: Schizophrenia, a devastating mental disorder, displays a wide range of cognitive impairments including attentional impairment. Prepulse inhibition (PPI), in which a startle response to a loud acoustic noise is reduced by a preceding auditory stimulus of a lower intensity, is impaired in schizophrenic patients and rats injected with apomorphine (APO) or phencyclidine (PCP) mimicking attentional deficits in schizophrenics. Here we examined therapeutic efficacy of a newly developed atypical antipsychotic compound (YKP1447;YKP) on PPI impairment induced by various doses of APO and PCP. METHODS: This study was composed of 3 experiments. YKP (0.5-15 mg/kg) or vehicle (VEH) was administered 15 min before the injection of APO (0.5 mg/kg, Exp1) or PCP (2.0 mg/kg, Exp2:1.5 mg/kg, Exp3). They were then tested for PPI in which a mix of startle stimulus and prepulse was presented. RESULTS: APO or PCP treatment effectively impaired PPI in tested animals (VEH/APO or VEH/PCP). Impaired PPI in APO group was reversed in animals that were pretreated with YKP (5-10 mg/kg) (Exp1). However YKP treatment was not effective in PCP group (Exp2-3). CONCLUSION: High concentration of YKP pretreatment had antipsychotic effect on APO-induced impairment in attentional function suggesting that the compound could potentially be used to treat cognitive impairment due to increased dopaminergic receptorbinding.
Acoustics
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Animals
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Antipsychotic Agents
;
Apomorphine
;
Humans
;
Mental Disorders
;
Noise
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Phencyclidine
;
Rats
;
Schizophrenia
7.Influence of Glutamate on the Circling Movement In the Unilateral Substantia Nigra-lesioned Rats.
Myeong Il HAN ; Young Chul CHUNG ; Hong Bai EUN
Journal of Korean Neuropsychiatric Association 1997;36(5):919-926
The aim of this study was to examine the effects of various concentrations of glutamate(10(-8), 10(-6) and 10(-4) M) on the circling movement induced by apomorphine in the unilateral substantia nigra-lesioned rats. Subcutaneous apomorphine(0.1 mg/kg) elicited contralateral circling movement(641.7+/-163.9/hr), Glutamate(10(-6)-10(-4) M) significantly reduced the numbers of apomorphine-induced circling movement. This reducing effect of glutamate was antagonized and/or reversed by 10(-7) M GABA antagonist bicuculline. These results suggest that glutamate reduces circling movement induced by apomorphine and this reducing effect of glutamate may be mediated by increased GABA concentration in striatum and substantia nigra.
Animals
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Apomorphine
;
Bicuculline
;
Dopamine
;
GABA Antagonists
;
gamma-Aminobutyric Acid
;
Glutamic Acid*
;
Rats*
;
Substantia Nigra
8.Pharmacokinetics, Efficacy, and Safety of Selective Inhibitors of Phosphodiesterase Type 5 and Sublingual Apomorphine for the Treatment of Erectile Dysfunction.
Korean Journal of Andrology 2002;20(3):113-125
Oral pharmacotherapy has become the first-line therapy for the majority of patients with erectile dysfunction (ED) of broad-spectrum etiology since the introduction of oral sildenafil, a potent, selective inhibitor of phosphodiesterase type 5 (PDE5). More than 3 years following the launch of sildenafil have made us informed fully about the mechanism of sildenafil, its clinical efficacy and safety, and appropriate use of the drug. Recently, the efficacy and tolerability of another potent, selective inhibitors of PDE5, vardenafil and tadalafil have been reported one after another and their phase 3 clinical studies worldwide have just finished. The PDE5 inhibitors are contraindicated in patients taking nitrates and may be restricted in others. The recent introduction of sublingual (SL) apomorphine, a centrally acting dopaminergic agonist with known erectogenic effects, could provide patients and clinicians with an additional option in the treatment of ED, although its efficacy and safety need to be verified further by worldwide clinical studies. We are in face of the era of multiple oral agents available for the treatment of ED. Due to the complex nature of individual patient-oriented goals and the multifactorial nature of ED, choices are needed that can be adapted to the requirements and responses of the individual patients. In this review, an overview of the pharmacokinetics, efficacy and safety of the oral PDE5 inhibitors, sildenafil, vardenafil and tadalafil, and sublingual apomorphine are provided.
Apomorphine*
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Dopamine Agonists
;
Drug Therapy
;
Erectile Dysfunction*
;
Humans
;
Male
;
Nitrates
;
Pharmacokinetics*
;
Phosphodiesterase 5 Inhibitors
9.Proerectile Effects of Selective alpha1 Blockers: A Comparative Study with Rat Model.
Jung Min SIM ; Kwanjin PARK ; Jae Seung PAICK
Korean Journal of Urology 2003;44(11):1149-1156
PURPOSE: The purpose of this study was to investigate the pro-erectile potential of various urethral alpha blockers using pharmacological or electrical induction of erection in anesthesized rats. MATERIALS AND METHODS: To evaluate the influence on centrally mediated erection, intravenous administeration of terazosin, doxazosin(3, 10, 30microgram/kg), and tamsulosin (0.3, 1, 3microgram/kg), followed by submaximal subcutaneous apomorphine(50microgram/kg) administration, mean arterial pressure(MAP) and intracavernosal pressure(ICP) were recorded over 30 minutes in male anesthesized rats. The time to first response, peaks within 30 minutes, maximal ICP, area under the curve, percentage of ICP/MAP were compared. To evaluate the influence on peripherally induced erections, various doses of alpha antagonists and submaximal cavernous nerve stimulation(0.5ms, 2V, 10Hz) were combined. The ICP increase and ICP/MAP percentage were also compared. RESULTS: Although various dose response relationships were shown, all three alpha blockers enhanced erectile activity triggered by apomorphine. In terms of time to first response and peaks within 30 minutes, the proerectile effects of terazosin was most prominent whereas those of tamsulosin was minimal, requiring larger doses. In combining with cavernous nerve stimulation, doxazosin and tamsulosin showed moderate proerectile activity, but the highest dose of terazosin was required to enhance ICP increase induced by cavernous nerve stimulation. Despite their pressure lowering effects, all tested alpha adrenergic blockers significantly enhanced the ICP/MAP percentage. CONCLUSIONS: The present finding clearly indicated that alpha 1 selective antagonists can enhance erectile capacity when combined with central or peripheral stimuli for erection.
Adrenergic alpha-Antagonists
;
Adrenergic Antagonists
;
Animals
;
Apomorphine
;
Doxazosin
;
Humans
;
Male
;
Models, Animal*
;
Rats*
10.The Clinical Trial of Apomorphine Hydrochloride SL(Uprima(r)) in Patients with Erectile Dysfunction.
Hyun Cheol PARK ; Hyun Jun PARK ; Nam Cheol PARK
Korean Journal of Urology 2003;44(10):1038-1044
PURPOSE: The clinical efficacy and safety of apomorphine hydrochloride SL, a new centrally acting oral agent for the management of the male erectile dysfunction (ED), were evaluated. MATERIALS AND METHODS: Sixty consecutive patients with ED, who visited the Male Sexual Dysfunction Clinic at Pusan National University Hospital, between April and December 2002, were evaluated by open labelled and uncontrolled randomized methods. Apomorphine hydrochloride SL (Uprima(r)), 4-8 3mg tablets, was prescribed on each visit, which was administered sublingually according to the standard patient guidelines. An overall evaluation of erectile function was performed using the international index of erectile function (IIEF) and global efficacy assessment questions (GAQ). RESULTS: The age distribution of the 51 cases was 22 to 76 years, with a mean of 47.6+/-10.6 years. During the mean follow-up period of 26.2+/-18.6 days, ranging from 7 to 156 days, the sum of the IIEF symptom scores changed significantly, from 11.2+/-6.7, at the baseline, to 17.0+/-8.2, on the 3rd visit (p>0.05). The IIEF scores were significantly improved in the Q3 and Q4, at 45.7% and 59.8%, respectively(p<0.05), while those in the Q6, Q10, Q12 and Q13 were not improved after treatment (p>0.05). The improvements in the IIEF scores revealed in psychogenic and mild grade ED were statistically significance (p<0.05). Selectivity as a treatment regimen was shown in only 5 cases (8.3%). Adverse reactions were noted in 7 cases (13.7%), but were self-limited, and resulted in only 1 (1.9%) drop-out due to dizziness. CONCLUSIONS: Apomorphine hydrochloride SL is suggested would be a proper oral agent in patients with psychogenic or mild degree organic ED.
Age Distribution
;
Apomorphine*
;
Busan
;
Dizziness
;
Erectile Dysfunction*
;
Follow-Up Studies
;
Humans
;
Male
;
Tablets