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PubMed2002

Apomorphine SL (Uprima): preclinical and clinical experiences learned from the first central nervous system-acting ED drug.

An exclusive central site of action for the proerectile effect of apomorphine, including not only the brain but also the spinal cord, is supported by extensive experimental data. Assuming that the mechanisms of action of apomorphine are similar in humans and animal models, its use for the treatment of erectile dysfunction (ED) validates the emerging idea that erectile response could be enhanced by acting directly within the central nervous system (CNS). It also emphasized the key role of the dopaminergic system in the control of erection. As exemplified with the clinical development of apomorphine, targeting the CNS does not rule out the occurrence of undesirable side effects. Because the rare event of syncope induced by apomorphine is not well understood, further research should be conducted to explore its possible mechanisms. In clinical practice, however, approved doses of apomorphine SL are well tolerated. It is noteworthy that no modification of sexual desire was observed with apomorphine. Indeed, drugs acting within the CNS may more likely interact with sexual desire than peripherally acting drugs, and care should be taken to assess this point in the future. Although our knowledge of the control of penile erection by the CNS is restricted, there are many potential sites for CNS-acting ED drugs. New centrally acting therapy for ED should concentrate on receptor targets more specific to erectile command. Clinical efficacy of new centrally-acting compounds will assess the well-founded purpose of this rationalization.

Animals↗
PubMedDate not supplied

Clinical efficacy of Apomorphine SL in erectile dysfunction of diabetic men.

Although subgroup analyses from large randomised premarketing studies have shown that Apomorphine SL enhances the percentage of erections firm enough for sexual intercourse in diabetic men, the clinical role of the drug in this patient population remains to be elucidated. The aim of the present study was to assess the efficacy of Apomorphine SL in diabetic males with erectile dysfunction (ED) and to identify factors predicting those who may benefit from the treatment. A total of 130 diabetic patients were randomised to receive either four tablets of 3 mg Apomorphine or a matching placebo. Assessments of efficacy comprised the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and the one-item global efficacy question (GEQ). Patients with both a positive response to the GEQ and an improvement of at least 5 points in the EF domain of the IIEF were considered responders and subanalysed by several parameters indicative of the severity of both ED and diabetes. Response rate was 17% after placebo and 22% after Apomorphine SL. The EF domain of the IIEF and both questions 3 and 4 scores did not significantly improve in either of the two arms over the baseline. A younger age and a lower Hb1Ac were significantly linked to the status of responder in the Apomorphine arm. Apomorphine SL failed to show a statistically significant benefit over a placebo, but 22% of patients had a clinically significant erectile response. These figures seem to suggest that the drug has a limited use for ED diabetic patients.

Apomorphine↗
PubMed2004

Apomorphine-induced prepulse inhibition disruption is associated with a paradoxical enhancement of prepulse stimulus reactivity.

Prepulse inhibition (PPI) refers to the reduction in startle reaction to a startle-eliciting stimulus when it is shortly preceded by a subthreshold prepulse stimulus. PPI has been extensively employed as an assay for sensorimotor gating, and its disruption has been characterized in specific disease conditions, including schizophrenia. In animals, dopamine agonists disrupt PPI, and this disruption can be antagonized by antipsychotic drug treatment. The present study extended these fundamental findings to C57BL6 mice, and further evaluated the subjects' reaction to the prepulse stimulus alone in relation to the expression of PPI. Not only did apomorphine (2.0 mg/kg, intraperitoneal (i.p.)) attenuate PPI but it also enhanced reactivity to the prepulse stimulus. The dual effects of apomorphine appear paradoxical in view of the positive correlation, detectable in both the control and apomorphine groups, between prepulse reactivity and PPI magnitude. The present findings contradict the hypothesis that apomorphine disrupts PPI via reduced detectability or perception of the prepulse, and we further propose that enhanced distractibility may provide a parsimonious account for the dual effects of apomorphine. Moreover, haloperidol pretreatment (0.4 mg/kg, i.p.) fully antagonized the effects of apomorphine upon prepulse reactivity as well as on PPI. The present results add to our understanding of the relevance and applicability of the PPI paradigm in modeling schizophrenia-like symptoms in animals.

Acoustic Stimulation↗
PubMed2006

Actions of novel antipsychotic agents on apomorphine-induced PPI disruption: influence of combined serotonin 5-HT1A receptor activation and dopamine D2 receptor blockade.

The dopamine D1/D2 agonist apomorphine (0.63 mg/kg) disrupted prepulse inhibition (PPI) of acoustic startle in rats, a model of sensorimotor gating deficits observed in schizophrenia. All current antipsychotics, which antagonize D2 receptors, prevent this apomorphine-induced deficit. A novel class of antipsychotics possesses, in addition to D2 antagonist property, various levels of 5-HT1A agonist activity. Considering that the latter itself produces PPI deficits, it appeared necessary to assess the potential of this novel class of antipsychotics to reverse apomorphine-PPI deficits. Potent D2 antagonists, like haloperidol (0.63-2.5 mg/kg), risperidone (0.63-10 mg/kg), and olanzapine (0.63-40 mg/kg) prevented apomorphine PPI disruption. The atypical antipsychotics, clozapine (40 mg/kg), nemonapride (0.01-2.5 mg/kg), ziprasidone (10 mg/kg), and aripiprazole (0.01 and 10 mg/kg), which all exhibit 5-HT1A agonist properties, reversed PPI deficits at some doses only, whereas the anti-dyskinetic agent sarizotan (0.16-10 mg/kg), an efficacious 5-HT1A agonist, did not. New generation antipsychotics with marked 5-HT1A agonist properties, such as SLV313 and SSR181507 (0.0025-10 mg/kg and 0.16-10 mg/kg, respectively) did not reverse these deficits whereas bifeprunox (0.04-2.5 mg/kg) did. To reveal the contribution of 5-HT1A agonist properties in the lack of effects of SLV313 and SSR181507, we pretreated rats with the 5-HT1A antagonist WAY100635 (0.63 mg/kg). Under these conditions, significant reversal of PPI deficit was observed, indicating that D2 antagonist properties of SLV313 and SSR181507 are now sufficient to overcome the disruptive effects of apomorphine. To summarize, antipsychotics possessing agonist efficacy at 5-HT1A receptors exhibit diverse profiles against apomorphine-induced PPI deficits, depending on the balance between D2 and 5-HT1A activities, suggesting that they may display distinct activity on some aspects of gating deficits in schizophrenic patients.

Aminopyridines↗
PubMed1993

Relation between clinical efficacy and pharmacokinetic parameters after sublingual apomorphine in Parkinson's disease.

Apomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the "on" period than 0.6 mg/kg (0.3 mg/kg: 24.2 +/- 14.6 min; 0.6 mg/kg: 86.7 +/- 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 +/- 3.4 min; 0.6 mg/kg: 38.3 +/- 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 +/- 3.2 ng/ml; 0.6 mg/kg: 22.7 +/- 3.6 ng/ml; p < 0.01; AUC: 0.3 mg/kg: 929 +/- 109 ng/ml/min; 0.6 mg/kg; 2,277 +/- 209 ng/ml/min; p < 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, and Cmax (r = 0.86, p < 0.01 for AUC; r = 0.63, p < 0.05 for Cmax). These results show that sublingual apomorphine could be of interest in the treatment of "off" phases in parkinsonian patients with motor fluctuations.

Administration, Sublingual↗
PubMed1996

Intranasal apomorphine rescue therapy for parkinsonian "off" periods.

Eleven patients with levodopa-related motor fluctuations were scored before and after intranasal apomorphine monotherapy, and the motor responses were compared with those with levodopa/carbidopa in this openlabel study. Oral trimethobenzamide was used to prevent apomorphine-induced nausea. Three measures of motor performance were employed: (a) the Unified Parkinson's Disease Rating Scale (UPDRS) motor battery; (b) a timed hand-tapping test; and (c) the Webster's step-seconds test. The magnitude of the motor-score improvement after apomorphine administration was very similar to that after the usual doses of levodopa/carbidopa in the 10 patients completing the study; this was true for all three outcome measures. A major advantage of apomorphine was the rapid onset of clinical response, which typically occurred in < 10 min, as well as the ease of administration. Major side effects, beyond those experienced with levodopa/carbidopa, were limited to nausea and vomiting (three patients) and orthostatic hypotension (one patient); however, only a single patient dropped out of the study as a consequence. These results indicate that intranasal apomorphine is effective in rapidly relieving parkinsonian "off" states and that, for most patients, trimethobenzamide is an effective and well-tolerated antiemetic for use with apomorphine.

Administration, Intranasal↗
PubMed2001

Apomorphine-induced changes in synaptic dopamine levels: positron emission tomography evidence for presynaptic inhibition.

The authors developed a novel positron emission tomography method to estimate changes in the synaptic level of dopamine ([DA]) induced by direct dopamine agonists (for example, apomorphine) in patients with Parkinson disease. The method is based on the typical asymmetry of the nigrostriatal lesion that often occurs in Parkinson disease. Using the between-side difference (ipsilateral (I) and contralateral (C) putamen to the more affected body side) of the inverse of the putamen [11C]raclopride binding potential (BP), the authors obtained [equation: see text] at baseline (that is, before apomorphine administration) and [equation: see text] after apomorphine administration (assuming the concentration of apomorphine is equal in both putamina). The between-side difference in the estimated synaptic concentration of dopamine (diff[DA]) should remain constant unless apomorphine affects dopamine release differently between the two sides. The authors found that apomorphine given subcutaneously at doses of 0.03 and 0.06 mg/kg induced significant changes in their estimate of diff[DA] (P < 0.05). Such changes were more pronounced when only patients with a stable response to levodopa were considered (P < 0.01). These findings provide in vivo evidence that direct dopamine agonists can inhibit the release of endogenous dopamine. The authors propose that this effect is mainly mediated by the activation of presynaptic D2/D3 dopamine receptors.

Antiparkinson Agents↗
PubMed1975

Comparison of the effect of apomorphine and L-DOPA on serum growth hormone levels in normal men.

Apomorphine hydrochloride (0.75 mg s.c.) has been compared with L-dopa (500 mg p.o.) in their effects on growth hormone secretion in a double blind cross-over study involving nine healthy men. Apomorphine increased serum GH levels above 10 ng/ml in all nine subjects 30-60 min after injection. In contrast, only six of these subjects showed a similar elevation with L-DOPA and in only three had the level increased above 6 ng/ml by 60 min. One subject failed to respond to L-dopa and in two others the peak was less than 6 ng/ml. GH levels were significantly higher at 30, 45 and 60 min following apomorphine than following L-dopa. Apomorphine-induced GH release was not related to changes in serum cortisol or blood sugar. Benztropine mesylate (1 mg i.m.) had no effect on apomorphine-induced GH release. These results suggest: (a) apomorphine may have advantages over L-dopa as a provocative agent to assess GH secretory capacity; (b) a dopaminergic mechanism subserves GH secretion; (c) cholinergic mechanisms do not antagonize dopaminergic-related GH release.

Adult↗
PubMed2004

Efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction. A comparative crossover study.

To compare the efficacy of apomorphine and sildenafil in men with nonarteriogenic erectile dysfunction (ED), 40 men were studied. Post-injection penile peak systolic velocity was greater than 25 cm s(-1). Twenty men started on apomorphine 2 mg and 20 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg, respectively, if necessary. After a 1-week washout period each group switched to the other treatment mode. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on an event log data. The majority (85%) of the men had concomitant diseases, risk factors for ED and 95% were heavy smokers. The overall success rate of apomorphine was 62.7%, compared with 73.1% of sildenafil (Yates-corrected chi-square, P < 0.0004). The response to apomorphine 2 mg and sildenafil 50 mg was age related. Sildenafil was statistically more effective than apomorphine in impotent men with normal penile Doppler. Given the contraindication of sildenafil in men taking nitrates and the quick time of action of apomorphine, the two drugs are satisfactory first line therapeutic tools in such individuals and the choice should be based on patient's needs and preferences.

Apomorphine↗
PubMed1981

Effect of nicotinic and muscarinic drugs on amphetamine- and apomorphine-induced circling behaviour in rats.

The effect of drugs modulating the activity of nicotinic or muscarinic cholinergic receptors on the circling behaviour induced by amphetamine and apomorphine in rats with unilateral 6-hydroxydopamine lesion of nigrostriatal dopaminergic pathway was studied. Nicotine (0.2 mg/kg subcutaneously) significantly increased amphetamine-induced circling behaviour and tended to inhibit apomorphine-induced circling behaviour. Mecamylamine and pempidine (both 2 mg/kg intraperitoneally) slightly but significantly depressed the intensity of circling behaviour induced by amphetamine, but failed to modify the induced by apomorphine. Pilocarpine (10 mg/kg intraperitoneally) clearly inhibited both amphetamine- and apomorphine-induced circling behaviour. Unlike pilocarpine, atropine (10 mg/kg intraperitoneally significantly increases the intensity of the circling behaviour induced by amphetamine and also to some extent that induced by apomorphine. Neither hexamethonium (5 mg/kg intraperitoneally) nor methylatropine (1 mg/kg subcutaneously) modified the circling behaviour induced by either amphetamine or apomorphine. The results show that stimulation of central nicotinic and muscarinic receptors may have some opposite effects on the dopamine dependent circling behaviour. The presynaptic nicotinic cholinergic receptors on the terminals of the nigrostriatal dopaminergic neurones, stimulation of which may increase the release of dopamine, might be involved in the action of nicotinic drugs. The muscarinic cholinergic receptors in the striatum and/or in the substantia nigra might be involved in the action of muscarinic drugs.

Amphetamine↗
PubMed1987

Differential effects of the dopamine antagonist remoxipride on apomorphine induced behaviour in the rat.

The effects of the novel substituted benzamide remoxipride on apomorphine induced behaviour in rats was investigated by means of an automatic holeboard apparatus. The ability of remoxipride to antagonise locomotion and gnawing induced by a high dose of apomorphine (5 mg/kg) and inhibition of exploration induced by a low dose of apomorphine (0.05 mg/kg) was tested. It was found that remoxipride in moderate doses potentiate locomotion and inhibit gnawing induced by the high dose of apomorphine while higher doses of remoxipride inhibits both apomorphine induced gnawing and locomotion. The inhibition of exploration following the low dose of apomorphine was not antagonised by remoxipride pretreatment. The results demonstrated that remoxipride has an interesting and unique profile of dopamine antagonistic effects in rat behavioural models.

Animals↗
PubMed1986

Concentration-response relations for apomorphine effects on heart rate in conscious rats.

The pharmacokinetics of apomorphine in plasma and brain tissue have been studied in relation to the time courses of effects on heart rate in conscious rats. The kinetic behaviour was investigated after 2 mg kg-1 i.v. and 5 mg kg-1 s.c., respectively. Apomorphine showed a high total plasma clearance (165-207 ml min-1 kg-1) and, despite a relatively large volume of distribution (3.4-4.1 litre kg-1), a biological half-life of about 14 min was obtained irrespective of route of administration. The kinetics in whole brain were identical with those in plasma. Apomorphine produced biphasic effects on the heart rate during the time courses of subcutaneous single doses: a low dose (50 micrograms kg-1) induced pure bradycardia while the doses of 100 micrograms kg-1 and 5 mg kg-1 produced responses oscillating between bradycardia and tachycardia. When we evaluated the relation between apomorphine concentrations and effects on the heart frequency with a composed sigmoid Emax model, apomorphine exhibited a U-shaped steady-state plasma concentration-response curve. Bradycardia appeared after low concentrations, reached a maximum and then decreased with increasing concentrations. A further augmentation of apomorphine concentration resulted in the opposite effect, i.e. tachycardia. Separate concentration-response curves for bradycardia and tachycardia were calculated. The changes in biophase concentration that occur during the absorption and disposition may thus cause the fluctuations between contrasting effects seen during the time course of a single dose.

Animals↗
PubMed1986

Effects of apomorphine and haloperidol in fetal lambs.

Injections of 100 micrograms apomorphine (I.A.) in intact unanaesthetized fetal lambs resulted in the onset of low-voltage electrocortical activity if not already present, onset or an increase in amplitude of fetal breathing movements, and in about 50% of experiments, onset or an increase in skeletal muscle activity. These responses also occurred during isocapnic hypoxia, though the stimulation of breathing was less than in normoxic lambs. Apomorphine had no consistent effects on the blood gases, pH, heart rate or blood pressure. In fetal lambs with the carotid nerves and vago-sympathetic trunks sectioned, apomorphine had the same effects as in intact lambs, except that there was a small fall in arterial O2 pressure (Pa,O2). Haloperidol (0.5-1 mg I.V.) had no effect on spontaneous breathing movements or electrocortical activity, but blocked all responses to apomorphine for several hours. Dopamine (up to 4 mg I.V.) caused an increase in arterial pressure accompanied by bradycardia, but had no effect on breathing movements or electrocortical activity. After suprapontine brain-stem transection, the electrocortical response to apomorphine was reduced. The respiratory response was lost or reversed, with apomorphine causing a reduction in amplitude of breathing. Haloperidol reduced the incidence of breathing movements for several hours in brain-stem-transected fetuses. We conclude that there is a central pathway, including at least one dopaminergic synapse and with components above the pons, which can stimulate fetal motor activity and breathing. It does not appear to be tonically active and its normal function is unknown.

Animals↗
PubMed1976

Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy.

Serum growth hormone (GH) and prolactin (PRL) concentrations were measured after administration of the dopamine receptor agonist, apomorphine HC1 (0.75 mg subcutaneously), to 17 chronic schizophrenic patients, four of whom had an oral dyskinesia, who were withdrawn from chronic neuroleptic therapy for periods of two to 15 weeks, and in 21 control subjects (normal volunteers or physically healthy alcoholics not exposed to neuroleptics). Six of the schizophrenic patients, but none of the controls, had raised baseline levels of GH (greater than 6 ng/ml). After apomorphine all controls showed an increase in serum GH with a peak concentration of 9 ng/ml or more, whereas eight subjects withdrawn from neuroleptics showed an inadequate response (peak less than 6 ng/ml) and in two others an inadequate response was obtained on one of two trials. The peak GH concentration was significantly less after apomorphine in patients withdrawn from neuroleptics (11.90 +/- 3.19 ng/ml) compared with controls (20.80 +/- 2.11 ng/ml) (P less than 0.05). Among patients withdrawn from neuroleptics, those with an oral dyskinesia had significantly lower peak GH concentration 2.46 +/- 0.93 ng/ml) after apomorphine compared with those without (14.85 +/- 3.83 ng/ml) (P less than 0.05). There were no differences in serum PRL concentrations, before or after apomorphine administration, between patients withdrawn from neuroleptics and controls. In uncontrolled observations none of the four patients with an oral dyskinesia showed any worsening of the movement disorder after apomorphine. These data provide no evidence for supersensitivity of dopamine receptors in chronic schizophrenic patients withdrawn from chronic neuroleptic therapy.

Adult↗
PubMed2000

Systematic review of acute levodopa and apomorphine challenge tests in the diagnosis of idiopathic Parkinson's disease.

OBJECTIVES: To perform a systematic review of studies examining the diagnostic accuracy of acute challenge tests with levodopa and/or apomorphine in parkinsonian syndromes to assess their value in the diagnosis of idiopathic Parkinson's disease. METHODS: A literature search including Medline and the Cochrane Library was performed for studies published in any language comparing acute levodopa and/or apomorphine response with chronic levodopa therapy in parkinsonian syndromes. Abstracted sensitivity and specificity data were summarised using variance weighting and conditional logistic regression for studies comparing two challenge tests. RESULTS: Thirteen studies were located: four examining de novo patients and nine examining patients with well established idiopathic Parkinson's disease and non-parkinsonian conditions. Despite the significant heterogeneity in the methodologies employed, the comparable results suggest that this had little effect on the accuracy of the tests. The sensitivity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.86 (95% confidence interval (95% CI) 0.78-0.94), acute levodopa 0.75 (95% CI 0.64-0.85), and chronic levodopa therapy 0.91 (95% CI 0.85-0.99). The specificity for the diagnosis of established idiopathic Parkinson's disease was: apomorphine 0.85 (95% CI 0.74-0.96), acute levodopa 0.87 (95% CI 0. 77-0.97), and chronic levodopa therapy 0.77 (95% CI 0.61-0.93). The number of patients positive for each test divided by the number with clinically diagnosed de novo disease was: apomorphine 0.63 (95% CI 0. 56-0.70), acute levodopa 0.69 (95% CI 0.59-0.80), and chronic levodopa therapy 0.76 (95% CI 0.70-0.82). CONCLUSIONS: The accuracy of the acute levodopa and apomorphine challenge tests is similar to, but not superior than, that of chronic levodopa therapy in the diagnosis of idiopathic Parkinson's disease. As most patients will be given chronic dopamimetic therapy, these tests add nothing while causing significant adverse events and additional cost.

Apomorphine↗
PubMed1975

The effect of apomorphine and ergocriptine on the release of MSH by the pars intermedia of Rana pipiens.

In an attempt to further characterize the nature of the innervation controlling melanophore-stimulating hormone (MSH) release from the pars intermedia (PI), pellets containing either apomorphine or ergocriptine were implanted in contact with the PI of the frog, and the effect on the animal's coloration was observed. Frogs with apomorphine implants exhibited skin pallor for several hours and those with ergocriptine implants were pallid for a few days. Hypophysectomized (HX) frogs which had been darkened with MSH regained their pallor no sooner when given an injection of apomorphine than with the vehicle. However, intact dark frogs lightened when injected with apomorphine. Frogs darkened by autotransplantation of the PI to the dorsal lymph sac were lightened by an injection of apomorphine. Frogs lightened by an ergocriptine implant on the PI and then darkened by MSH did not lighten sooner than HX frogs given an injection of MSH. Ergocriptine-containing pellets implanted in the thigh took longer to produce the same effect than those implanted in contact with the PI. Since apomorphine is known to stimulate dopamine receptors in the central nervous system, and there is some evidence that ergocriptine does also, the above evidence supports the hypothesis that dopamine receptors are present in the PI.

Animals↗
PubMed2003

Apomorphine attenuates 6-hydroxydopamine-induced apoptotic cell death in SH-SY5Y cells.

Enhanced oxidative stress is implicated in the pathogenesis of Parkinson's disease. The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) induces the production of reactive oxygen species (ROS), leading to neuronal cell death. On the other hand, apomorphine, a dopamine D1/D2 receptor agonist and known as a potent antioxidant, has been reported to have a neuroprotective effect. In the present study, we investigated the effect of apomorphine on 6-OHDA-induced apoptotic cell death using the human dopaminergic neuroblastoma cell line, SH-SY5Y. The co-treatment of cells with apomorphine significantly attenuated 6-OHDA-induced ROS generation, the phosphorylation of c-Jun N-terminal kinase (JNK), DNA fragmentation and subsequent apoptotic cell death. In addition, pretreatment with apomorphine for 24 h and the following concomitant treatment enhanced the protective effects against 6-OHDA-induced toxicity except for the attenuation of JNK phosphorylation. We also demonstrated that pretreatment alone with apomorphine for 24 h prior to the exposure confers resistance against 6-OHDA-induced cell toxicity. These findings suggested that apomorphine acts principally as a radical scavenger to suppress the level of ROS and ROS-stimulated apoptotic signaling pathway, whereas the other mechanisms might be involved in the protective effects.

Antiparkinson Agents↗
PubMed1992

Dopaminergic stimulation of oxytocin concentrations in the plasma of male and female monkeys by apomorphine and a D2 receptor agonist.

Administration of the dopamine receptor agonist apomorphine causes a dose-dependent increase in plasma oxytocin concentrations and dose-specific behavioral changes in rodents. To investigate whether dopamine receptor agonists will elicit similar neuroendocrine and behavioral effects in primates, we administered graded doses of apomorphine and the respective dopamine D1 and D2 receptor agonists, CY 208-243 and LY 163502, to monkeys and monitored plasma concentrations of oxytocin and behavior. Five female rhesus, two male rhesus, and two male cynomolgus monkeys had chronic indwelling venous catheters implanted and were maintained on standard jacket/tether/swivel systems to allow remote blood sample collection. During experiments, blood samples were collected 10 and 5 min before drug injection and at 2- to 120-min intervals after each injection. Apomorphine (50-400 micrograms/kg) and LY 163502 (10-100 micrograms/kg) elicited dose-dependent stimulations of oxytocin secretion. CY 208-243 (100-400 micrograms/kg) did not significantly affect oxytocin secretion. Low doses of apomorphine (50-100 micrograms/kg) and LY 163502 (10-25 micrograms/kg) elicited yawning, and high doses of apomorphine (200-400 micrograms/kg) and LY 163502 (50-100 micrograms/kg) elicited stereotypic behaviors. No behavioral effects of CY 208-243 (100-400 micrograms/kg) were observed. The magnitude of the oxytocin secretory responses varied among animals, but was similar in male and female monkeys. In summary, apomorphine and LY 163502 both elicited dose-related stimulation of oxytocin secretion coupled with dose-specific behavioral changes in male and female monkeys, while no effects of CY 208-243 on these parameters were observed. We conclude that dopamine receptor agonists, and in particular D2 agonists, may be useful tools for studies exploring the physiological and behavioral actions of oxytocin in primates.

Animals↗