No abstract available.
Animals ; Apomorphine* ; Brain* ; Rats*

No abstract available.
Animals ; Apomorphine* ; Dopamine* ; Parkinsonian Disorders* ; Rats* ; Receptors, Dopamine D2*

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 ; Apomorphine ; Ganglion Cysts ; Models, Animal* ; Neural Pathways* ; Neurons ; Rats*

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 ; Apomorphine ; Bicuculline ; Dopamine ; GABA Antagonists ; gamma-Aminobutyric Acid ; Glutamic Acid* ; Rats* ; Substantia Nigra

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 ; Apomorphine ; Dopaminergic Neurons ; Oxidopamine ; Rats* ; Tissue Transplantation* ; Transplantation ; Transplants* ; Tyrosine 3-Monooxygenase

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* ; Dopamine Agonists ; Drug Therapy ; Erectile Dysfunction* ; Humans ; Male ; Nitrates ; Pharmacokinetics* ; Phosphodiesterase 5 Inhibitors

BACKGROUND: Apomorphine-induced rotational behavior of unilateral 6-hydroxydopamine (OHDA) lesioned rat is widely used to develop anti-Parkinsonian treatments including drugs, neuroprotective therapy, and neural graft. Time course of changes in rotational behavior after lesioning, however, has not been fully elucidated. The aim of this study was to observe the chronological changes in the rotational response and to find the optimal period when this model is used for investigation of various therapies. METHODS: 6-OHDA was stereotaxically delivered to the unilateral substantia nigra in 13 rats. Rotational responses to apomorphine administrations were counted in the rotomotor on 2, 4, 8, 12, and 14 weeks after lesioning. RESULTS: The total turns for two hours increased continuously up to eight weeks, and then plateaued. CONCLUSIONS: Apomorphine-induced rotations increase until eight weeks after 6-OHDA lesioning. Therefore, this Parkinsonian model should be used at least eight weeks after lesioning. Even though priming was not excluded as an explanation in the experiment, we reason that progressive degeneration of dopaminergic neurons may explain the chronological changes in rotational behavior.
Animals ; Apomorphine* ; Dopaminergic Neurons ; Neuroprotective Agents ; Oxidopamine* ; Rats* ; Substantia Nigra ; Transplants

PURPOSE: The aim of this study was to demonstrate that the combined systemic administration of apomorphine (APO) and sildenafil have a synergistic effect on the erection in conscious rabbits. MATERIALS AND METHODS: The erections of the male New Zealand White rabbits (2-3kg, n=12) were assessed by measuring the length of the uncovered penile mucosa (LUPM) and duration of the erection, both before and after the intravenous administration of agents. After the injection of APO (0, 0.05, 0.1, 0.4mg/kg), sildenafil was administered intravenously in a dose-response manner (0.5, 1, 5mg/kg), followed by measurements for 0-120 minutes. In additional experiments, the effect of increasing the dosages of sildenafil, combined with APO, on blood pressure were evaluated. RESULTS: The intravenous administration of sildenafil caused a concentration dependent increase in the LUPM. There was a statistically significant increase in the LUPM with the administration of APO compared with no administration. The dosages of sildenafil and APO showing the greatest efficacy of sildenafil potentiation were 1mg/kg and 0.1 mg/kg, respectively. The intravenous administration of APO at a dose of 0.1mg/kg was more effective than those of 0.05 and 0.4mg/kg, with dosages of sildenafil of 0.5 and 1mg/kg. There was no additional increase in the duration of erection on the administration of APO. The intravenous administration of sildenafil caused a concentration dependent decrease in blood pressure, but there was no additional decrease on administration of the APO. CONCLUSIONS: We have shown that apomorphine elicits a stronger response on the erection induced by sildenafil in conscious rabbits, with no additional decrease in blood pressure.
Administration, Intravenous ; Apomorphine* ; Blood Pressure ; Humans ; Male ; Mucous Membrane ; Penile Erection* ; Rabbits* ; Sildenafil Citrate

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*

PURPOSE: The aim of this study was to demonstrate whether various stressful conditions have effects on the erection and manifestation of oxytocin positive neurons of the paraventricular nucleus (PVN) in mice. MATERIALS AND METHODS: Thirty, 10-weeks old mice were divided into 4 groups: control (A), stress only (B), apomorphine only (C) and apomorphine with stress treated (D) groups. Chronic restraint and forced swimming stresses were induced. Apomorphine (80ug/kg) was subcutaneously injected every 3 days, and after 14 days the brains of the mice were extracted, and treated with immunohistochemistry. The data were analyzed by optical density and Student's t-test. RESULTS: One of group D was died of excessive stress. The erection rates of groups C, D, A and B were 80, 64, 20 and 0%, respectively. The number of oxytocin-positive neurons in the PVN of groups C, A, D and B were 215, 205, 201 and 190, respectively (p=0.07). The optical density of the oxytocin-positive neurons of the erection group was significant higher than that of the non-erection group (125 vs. 105, p<0.01). CONCLUSIONS: The erectile function was decreased under stressful condition, which was improved by administration of apomorphine. Apomorphine has a relationship with the oxytocin-positive neurons in the PVN; therefore, it is one of the important factors in inducing an erection.
Animals ; Apomorphine* ; Brain ; Immunohistochemistry ; Mice* ; Neurons* ; Oxytocin* ; Paraventricular Hypothalamic Nucleus ; Swimming