Doses Of Apomorphine Research Articles

Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14–42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

Use of abdominal thrusts is associated with improved rates of successful emesis induction in dogs.

To evaluate the effect of abdominal thrusts as a synergistic procedure to IV apomorphine administration on the occurrence and rate of onset of successful induction of emesis in dogs. 31 client-owned dogs. Dogs in which induction of emesis via IV apomorphine was prescribed by the attending clinician were prospectively randomized to either receive abdominal thrusts performed by a nurse or clinician or to have no physical interventions performed following IV apomorphine administration. Data collected included signalment, weight, reason for emesis, time from suspected ingestion to presentation, time from the dog's last meal to presentation, dose of apomorphine administered in milligrams, and time from apomorphine administration to emesis. Emesis induction was successful in 14 of 14 (100%) of the dogs in the abdominal thrust group and 13 of 17 (76.5%) in the control group (P = .02). In dogs with successful emesis, median time to emesis was 90.5 seconds (range, 36 to 348 seconds) in the abdominal thrust group and 106 seconds (range, 37 to 360 seconds) in the control group (P = .29). Abdominal thrusts were associated with an increased frequency of successful emesis in dogs following IV apomorphine, but did not shorten the rate of onset of emesis in dogs that vomited. Application of abdominal thrusts may be beneficial in dogs in which emesis is indicated and that do not have a clear contraindication.

Morphine and dopamine: Low dose apomorphine can prevent both the induction and expression of morphine locomotor sensitization and conditioning

The disinhibition of dopamine neurons in the VTA by morphine is considered an important contributor to the reward potency of morphine. In this report, three experiments were conducted in which a low dose of apomorphine (0.05 mg/kg) was used as a pretreatment to reduce dopamine activity. Locomotor hyperactivity was used as the behavioral response to morphine (10.0 mg/kg). In the first experiment, five treatments with morphine induced the development of locomotor and conditioned hyperactivity that were prevented by apomorphine given 10 min prior to morphine. Apomorphine before either vehicle or morphine induced equivalent reductions in locomotion. In the second experiment, the apomorphine pretreatment was initiated after induction of a conditioned hyperactivity and apomorphine prevented the expression of the conditioning. To assess the effects of apomorphine on VTA and the nucleus accumbens, ERK measurements were carried out after the induction of locomotor and conditioned hyperactivity. Increased ERK activation was found and these effects were prevented by the apomorphine in both experiments. A third experiment was conducted to assess the effects of acute morphine on ERK before locomotor stimulation was induced by morphine. Acute morphine did not increase locomotion, but a robust ERK response was produced indicating that the morphine-induced ERK activation was not secondary to locomotor stimulation. ERK activation was again prevented by the apomorphine pretreatment. We suggest that contiguity between the ongoing behavioral activity and the morphine activation of the dopamine reward system incentivizes and potentiates the ongoing behavior generating equivalent behavioral sensitization and conditioned effects.

Apomorphine for the Treatment of Erectile Dysfunction: Systematic Review and Meta-Analysis.

Sublingual apomorphine could be an option in patients with erectile dysfunction who cannot take phosphodiesterase type 5 inhibitors (e.g., using nitrates). We have completed a systematic review to evaluate the effects of sublingual apomorphine comparing with placebo for treating erectile dysfunction. The evidence searching process finished on 9 January 2019. We included nine randomized controlled trials (RCTs). Treatment length varied from 4 to 8weeks and doses ranged from 2 to 6mg. The percent of successful sexual intercourse attempts per ingested dose of apomorphine was evaluated in eight studies. All the studies found that apomorphine was better than placebo (6-27% more successful intercourse attempts than with placebo), but differences were not statistically significant in one study done in patients previously treated with radical prostatectomy. Regarding erectile function scores, three studies reported higher improvement on the erectile function scores for apomorphine. Differences with placebo were not clinically relevant in another two studies, one in which only diabetic patients were included and one in which only patients with radical prostatectomy were involved. Discontinuation of treatment due to adverse events was higher for apomorphine, particularly for higher doses. Available evidence suggests that sublingual apomorphine is more effective than placebo, except for patients previously treated with radical prostatectomy, and is generally well tolerated at doses of 2 or 3mg. Nowadays, sublingual apomorphine is the only licensed oral drug for erectile dysfunction not absolutely contraindicated with nitrates use, and more RCTs should be performed to evaluate its effects and safety for treating ED.

Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson\u2019s disease

Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson’s disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median “off”-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.

The pesticide fipronil injected into the substantia nigra of male rats decreases striatal dopamine content: A neurochemical, immunohistochemical and behavioral study

Experimental evidence shows that the phenylpyrazole pesticide fipronil exerts neurotoxic effects at central level in rodents, and in particular on nigrostriatal dopaminergic neurons, whose degeneration is well known to cause motor and non-motor deficits in animals and in humans. In order to characterize better the central neurotoxic effect of fipronil, we injected fipronil (15 and 25 μg) dissolved in dimethyl sulfoxide (DMSO) unilaterally into the substantia nigra of male rats. Male rats injected with DMSO unilaterally into the substantia nigra were used as controls. Control and fipronil-treated rats were then tested in different motor (i.e., open field arena, rotarod, tail flick) and non motor tests (novel object recognition, social interaction) 15 days after injection. A systemic challenge dose of the dopamine-agonist apomorphine was also used to study the presence of a rotational behavior. Sixteen days after fipronil or DMSO injection into the substantia nigra, rats were sacrificed, and either striatal dopamine content or substantia nigra tyrosine hydroxylase (TH) immunoreactivity were measured. The results confirm that the unilateral injection of fipronil into the substantia nigra caused the degeneration of nigrostriatal dopaminergic neurons, which leads to a decrease around 50 % in striatal dopamine content and substantia nigra TH imunoreactivity. This occurred together with changes in motor activity and coordination, and in nociception but not in recognition memory and in social interaction, as revealed by the results of the behavioral experiments performed in fipronil-treated rats compared to vehicle-treated rats 15 days after treatment, as found with other compounds that destroy nigrostriatal dopaminergic neurons.

Efficacy of intravenous administration of apomorphine for removal of gastric foreign material in dogs: 495 cases (2010–2015)

To evaluate the efficacy of IV administration of apomorphine for removal of gastric foreign bodies in dogs. 495 dogs with gastric foreign bodies. Records of a veterinary hospital were searched to identify dogs that received an injectable formulation of apomorphine between January 1, 2010, and July 30, 2015. Dogs with a gastric foreign body that received an IV injection of apomorphine were included in the study. Information extracted from the record of each dog included signalment, type of foreign material ingested, duration between foreign material ingestion and emesis, dose and number of doses of apomorphine administered, and whether emesis occurred and did or did not result in successful removal of the foreign body. Descriptive data were compared between dogs with and without successful foreign body removal. Emesis with successful foreign body removal was achieved in 363 and 11 dogs after administration of 1 and 2 doses of apomorphine, respectively. Successful removal was more likely for young dogs and dogs that had ingested fabric, leather, or bathroom waste. Successful removal was less likely as the duration between foreign body ingestion and emesis increased and for dogs that received opioids, sedatives, or antiemetics before apomorphine administration. Minor adverse effects were recorded for only 4 dogs. IV administration of apomorphine was a viable alternative for induction of emesis and removal of gastric foreign bodies in dogs. Dogs should be examined as soon as possible after foreign body ingestion and should not receive any medications that might affect apomorphine efficacy.

Continuous subcutaneous apomorphine monotherapy in Parkinson's disease.

Continuous subcutaneous apomorphine (APO) treatment is one of the 3 therapeutic options for advanced Parkinson's disease (PD), in addition to deep brain stimulation (DBS) and intrajejunal levodopa. Data from previously performed studies show that few PD patients can achieve APO infusion as monotherapy. The current pilot study presents the authors' experience in achieving APO monotherapy. During the last 2 years, 9 patients with APO were treated in the Department of Neurology of the Medical University of Lublin; each patient was offered a 5-day duration APO treatment as monotherapy. The main indication for the APO therapy was advanced PD with motor fluctuations and the patient's non-agreement for DBS therapy. Mean age of treated patients - 65.11 years, mean disease duration - 7.67 years, mean Hoehn-Yahr - 2.67, mean L-dopa equivalent before APO treatment - 1751.11 mg, mean daily dose of apomorphine as monotherapy - 106.11 ± 14.09 mg. All treated patients managed to achieve APO monotherapy. A statistically significant reduction was found in the duration of the 'off' states in the observed PD patients on APO monotherapy (p<0.05). No significant improvement was observed in the III motor score of the UPDRS on APO treatment, compared to optimized oral therapy used before APO treatment. APO monotherapy can be achieved in advanced PD, and seems to be a good therapeutic option for this group of patients, especially in that it allows a significant reduction in the off-time which significantly simplifies the drug regime. Nevertheless, hospital admission with experienced neurologist supervision is recommended when establishing a PD patient's APO monotherapy.

Sensor-based gait analysis of individualized improvement during apomorphine titration in Parkinson's disease.

Mobile, sensor-based gait analysis in Parkinson's disease (PD) facilitates the objective measurement of gait parameters in cross-sectional studies. Besides becoming outcome measures for clinical studies, the application of gait parameters in personalized clinical decision support is limited. Therefore, the aim of this study was to evaluate whether the individual response of PD patients to dopaminergic treatment may be measured by sensor-based gait analysis. 13 PD patients received apomorphine every 15min to incrementally increase the bioavailable apomorphine dose. Motor performance (UPDRS III) was assessed 10min after each apomorphine injection. Gait parameters were obtained after each UPDRS III rating from a 2×10m gait sequence, providing 41.2 ± 9.2 strides per patient and injection. Gait parameters and UPDRS III ratings were compared cross-sectionally after apomorphine titration, and more importantly between consecutive injections for each patient individually. For the individual response, the effect size Cohen's d for gait parameter changes was calculated based on the stride variations of each gait sequence after each injection. Cross-sectionally, apomorphine improved stride speed, length, gait velocity, maximum toe clearance, and toe off angle. Between injections, the effect size for individual changes in stride speed, length, and maximum toe clearance correlated to the motor improvement in each patient. In addition, significant changes of stride length between injections were significantly associated with UPDRS III improvements. We therefore show, that sensor-based gait analysis provides objective gait parameters that support clinical assessment of individual PD patients during dopaminergic treatment. We propose clinically relevant instrumented gait parameters for treatment studies and especially clinical care.

Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomised, placebo-controlled trial

Subcutaneous apomorphine infusion is a clinically established therapy for patients with Parkinson's disease with motor fluctuations not optimally controlled by oral medication. Open-label studies have shown that apomorphine infusion is effective in reducing off time (periods when antiparkinsonian drugs have no effect), dyskinesias, and levodopa dose, but confirmatory evidence from double-blind, controlled studies is lacking. We aimed to investigate the efficacy and safety of apomorphine infusion compared with placebo in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal treatment. In this randomised, placebo-controlled, double-blind, multicentre trial, we enrolled patients at 23 European hospitals who had been diagnosed with Parkinson's disease more than 3 years previously and had motor fluctuations not adequately controlled by medical treatment. Patients were randomly assigned (1:1) with a computer-generated randomisation code, stratified by site, to receive 3-8 mg/h apomorphine or placebo saline infusion during waking hours (16 h a day [range 14-18 was acceptable]) for 12 weeks. The flow rate of the study drug and other oral medications could be adjusted during the first 4 weeks on the basis of individual efficacy and tolerability, after which patients entered an 8-week maintenance period. The primary endpoint was the absolute change in daily off time based on patient's diaries, and was assessed in the full analysis set, which was defined as all patients who received at least one dose of allocated study drug and had efficacy data available at any timepoint post-baseline. Safety was assessed in all patients who received at least one dose of apomorphine or placebo. All study participants and investigators were masked to treatment assignment. Both the 12-week double-blind phase and the 52-week open-label phase of this study are now complete; this paper reports results for the double-blind phase only. This study is registered with ClinicalTrials.gov (NCT02006121). Between March 3, 2014, and March 1, 2016, 128 patients were screened for eligibility and 107 were randomly assigned, of whom 106 were included in the full analysis set (n=53 in both groups). Apomorphine infusion (mean final dose 4·68 mg/h [SD 1·50]) significantly reduced off time compared with placebo (-2·47 h per day [SD 3·70] in the apomorphine group vs -0·58 h per day [2·80] in the placebo group; difference -1·89 h per day, 95% CI -3·16 to -0·62; p=0·0025). Apomorphine was well tolerated without any unexpected safety signals. Six patients in the apomorphine group withdrew from the study because of treatment-related adverse events. Apomorphine infusion results in a clinically meaningful reduction in off time in patients with Parkinson's disease with persistent motor fluctuations despite optimised oral or transdermal therapy. Britannia Pharmaceuticals.

A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models.

The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.

Interactive effects of morphine and dopamine receptor agonists on spatial recognition memory in mice.

Both opiates and dopamine play important roles in learning and memory. Although synergistic action between these two neurotransmitters has been found, their functional roles remain unclear. Here, low dose morphine (2.5mg/kg) and low dose dopamine receptor agonists (apomorphine 0.05mg/kg; SKF38393 0.01mg/kg; bromocriptine 0.05mg/kg), which have no effects on spatial recognition memory, were injected intraperitoneally into mice 30minutes before a memory test in a two-trial recognition Y-maze. The Y-maze is based on the innate tendency of rodents to explore novel environments and is therefore suitable for exploring the effects of morphine on learning and memory. Our results showed that both D1-like and D2-like dopamine receptor agonists dose-dependently impaired the retrieval of spatial recognition memory in the Y-maze, and co-administration of memory ineffective doses of apomorphine (0.05mg/kg), SKF38393 (0.01mg/kg), or bromocriptine (0.05mg/kg) and of morphine (2.5mg/kg) resulted in impaired spatial recognition memory retrieval in mice. These findings suggest the existence of interactions between morphine and dopamine receptor agonists in memory processing and that activation of the dopamine system might contribute to morphine-induced impairment of memory, which could provide insight into human addiction.

Continuous subcutaneous apomorphine infusion in Parkinson's disease patients with cognitive dysfunction: A retrospective long-term follow-up study

IntroductionContinuous apomorphine infusion (CAI) is an advanced therapy in fluctuating Parkinson's disease (PD). The use of CAI is controversial in PD patients with cognitive dysfunction including visual hallucinations (VHs), and orthostatic hypotension (OH). This study was set-up to analyze the effectiveness and safety of CAI in elderly PD patients with cognitive dysfunction. MethodsThis new-user cohort study identified fluctuating PD patients who started CAI treatment at the rehabilitation unit of Parkinson Expertise Center (RU-PEC) Groningen, from November 2004 until 2016. Efficacy and safety data included motor function, cognitive status, OH and VHs, and was analyzed retrospectively. Pre-existent non-motor symptoms were treated optimally before starting CAI. ResultsForty-five fluctuating PD patients (age: 70.9 ± 8.1 yrs, disease duration: 10.8 ± 4.8 yrs) were identified, with pre-existing cognitive dysfunction, VHs (71%), and OH (26%). During the stay at RU-PEC (median 52 days) apomorphine was successfully titrated without worsening of pre-existing VHs and OH. The mean daily apomorphine dose was 66 ± 28 mg, accompanied by a reduction of levodopa-equivalent daily dose (LEDD) with 17%. The duration of ON-time and OFF-time significantly improved with +2.36 h (25%) and −1.66 h (−45%), respectively, while dyskinesia duration did not change. During long-term follow-up (median of 26 months) VHs and OH worsened in 9 and 4 patients, which necessitated discontinuation in 4 cases. ConclusionThis study demonstrates that CAI is also an effective treatment in advanced PD patients with concomitant cognitive dysfunction including VHs and OH, provided that these comorbidities are treated adequately as well.

Neurochemical and behavioural effects of hypidone hydrochloride (YL-0919): a novel combined selective 5-HT reuptake inhibitor and partial 5-HT1A agonist.

Our previous studies revealed that hypidone hydrochloride (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI) and displays partial 5-HT1A receptor agonist properties, exerts a significant antidepressant effect in various animal models. The aim of present research was to further investigate the pharmacology of YL-0919. We first investigated the target profile of YL-0919 using [35 S]-GTPγS binding and microdialysis. To determine whether the 5-HT or noradrenergic systems are involved in the antidepressant-like effect of YL-0919, the 5-hydroxytryptophan (5-HTP)-induced head-twitch test and antagonism with a high dose of apomorphine were performed. Using the learned helplessness paradigm, the novelty suppressed feeding test, the Vogel-type conflict and elevated plus-maze test, we further verified the antidepressant-like and anxiolytic-like effects of YL-0919. The effects of YL-0919 on hippocampal long-term potentiation (LTP) and sexual behaviour were also evaluated. Data from the present study demonstrated that YL-0919 displays partial 5-HT1A receptor agonist properties, producing a greater impact on extracellular 5-HT levels than a conventional SSRI (fluoxetine), as well as significant antidepressant and anxiolytic effects. Furthermore, YL-0919 treatment rapidly influenced the synaptic plasticity (enhancing LTP) of rats. Finally, at doses close to those producing antidepressant-like effects, YL-0919 did not result in a marked inhibition of sexual function. These data suggest that YL-0919 is probably a fast-onset potent antidepressant with few side effects.

Apomorphine Subcutaneous Injection for the Management of Morning Akinesia in Parkinson's Disease.

BackgroundIn patients with motor fluctuations complicating Parkinson's disease (PD), delays in time‐to‐ON with levodopa are common. This open‐label study aimed to assess the effect of apomorphine on time‐to‐ON in PD patients with morning akinesia.MethodsThe safety population included 127 enrolled patients, and the full analysis set (FAS) included 88 patients. Patients completed a 7‐day levodopa baseline period recording their time‐to‐ON following each morning dose of levodopa. Patients were titrated to an optimal dose of apomorphine (2–6 mg) while taking trimethobenzamide antiemetic therapy. Apomorphine was injected each morning for a 7‐day treatment period and time‐to‐ON was self‐recorded in 5‐minute blocks. The primary efficacy variable was time‐to‐ON in the apomorphine treatment period versus the baseline levodopa period. Secondary assessments included and global impression scales. Safety and tolerability were assessed through adverse events (AEs).ResultsPatients receiving apomorphine achieved mean ± standard deviation (SD) time‐to‐ON 23.72 ± 14.55 minutes, reduced from 60.86 ± 18.11 minutes with levodopa (P < 0.0001). Dose failures (defined as time‐to‐ON >60 minutes) were more commonly reported with levodopa versus apomorphine (46% vs. 7% of diary entries, respectively).Secondary endpoints supported the primary efficacy findings, with significant improvements from levodopa baseline to apomorphine treatment period (all P < 0.0001). The most common AEs were nausea and dizziness. Most patients who discontinued because of AEs did so in the titration phase.ConclusionsApomorphine injections significantly reduced time‐to‐ON in PD patients experiencing delayed onset of their morning levodopa dose, and was well tolerated in most patients. After apomorphine treatment, fluctuating patients with morning akinesia experienced rapid and reliable improvement of time‐to‐ON.

High Oestradiol Replacement Reverses Response Memory Bias in Ovariectomised Female Rats Regardless of Dopamine Levels in the DorsalStriatum.

Oestrogens influence memory system bias in female rats such that high levels of oestrogen are associated with place (or spatial) memory use, and low oestrogen levels with response (or habitual) memory use. Moreover, striatal-dependent response memory is sensitive to dopamine transmission in the dorsal striatum, and oestrogens have been shown to affect dopamine release in that brain area. In the present study, the effects of oestrogens and dopamine transmission on multiple memory system bias were explored in ovariectomised rats receiving low or high 17β-oestradiol replacement under saline, autoreceptor-activating doses of the dopamine D2 receptor agonist, apomorphine (50 and 80μg/kg), or amphetamine (0.5mg/kg) administration. Furthermore, dorsal striatal dopamine release was measured after administration of the same drug conditions using invivo microdialysis. As expected, high oestradiol rats predominantly used place memory, whereas the opposite pattern was observed in low oestradiol rats. However, the high apomorphine dose statistically significantly altered memory bias in high oestradiol rats from predominant place to predominant response memory, with a similar trend in the low apomorphine dose and the amphetamine group. There was no effect of drugs on memory bias in low oestradiol rats. Rats with high oestradiol replacement receiving amphetamine exhibited greater dorsal striatal dopamine release than low oestradiol replacement rats, and this difference was amplified in the right hemisphere. Furthermore, a logistic regression analysis revealed that oestradiol, but not dorsal striatal dopamine levels, significantly predicted response memory bias. These findings provide further evidence that oestradiol modulates memory system bias, and also that memory bias is changed by systemic apomorphine administration. However, although oestradiol affects dopamine transmission in the dorsal striatum in a lateralised manner, this does not predict memory system bias.

A case series of rapid titration of subcutaneous apomorphine in Parkinson's disease

Subcutaneous apomorphine injections provide prompt relief of OFF periods, but are considered an underused therapy. One reason for this might be the perception of difficulty in initiating apomorphine therapy. Over the past 30 years of use, Parkinson’s nurses have built a wealth of experience in how to initiate apomorphine in patients with motor fluctuations. The authors present here a case series of 24 Parkinson’s patients whose apomorphine dose was rapidly titrated according to the practice of the Parkinson’s nurse overseeing the titration. Most patients were successfully and safely titrated within 2 hours, indicating that this rapid schedule may be useful in reducing patient distress and making better use of available resources, compared to the slower schedule than is suggested in the UK apomorphine prescribing information. Patients were successfully initiated in a wide variety of settings, including day hospitals and within their own homes.

Baseline disease severity not predictive of sublingual apomorphine (APL-130277) dose needed to convert a PD patient from the OFF to ON state

Objectives: APL-130277 is a sub-lingual film strip designed to acutely reverse Parkinson’s disease (PD) OFF episodes by delivering apomorphine via the oral mucosa. We evaluated whether baseline disease severity predicted the effective APL-130277 dose.

Baseline disease severity not predictive of sublingual apomorphine (APL-130277) dose needed to convert a PD patient from the off to on state

Objectives: APL-130277 is a sub-lingual film strip designed to acutely reverse Parkinson’s disease (PD) OFF episodes by delivering apomorphine via the oral mucosa. We evaluated whether baseline disease severity predicted the effective APL-130277 dose.

Motor and non-motor outcomes of continuous apomorphine infusion in 125 Parkinson's disease patients

IntroductionContinuous apomorphine infusion (CAI) is an effective treatment in fluctuating Parkinson's disease (PD). However, long-term efficacy and safety data of CAI are scarce. MethodsWe retrospectively reviewed long-term outcomes of CAI on motor and non-motor symptoms in a Dutch cohort of 125 PD patients. ResultsOur cohort (age: 65.8 ± 9.8 years, disease duration: 11.9 ± 5.7 years) had a mean daily dose of apomorphine of 66 ± 30 mg, thereby reducing the levodopa-equivalent daily dose (LEDD) by 20%. The mean duration of treatment with apomorphine was 32.3 ± 31.9 months, ranging up to 139 months. Three-quarters of patients discontinued within the first four years. The main reason for discontinuation was a decreasing therapeutic effect. Patients who stopped apomorphine within four years had a lower LEDD reduction at hospital discharge and at last follow-up compared to patients who continued for a longer period. CAI showed good effects on motor fluctuations and dyskinesia, with better outcomes in patients with more pronounced LEDD reduction. CAI could be safely applied in patients with pre-existing visual hallucinations (30%). ConclusionCAI showed beneficial effects on motor and several non-motor symptoms, whereas the magnitude of LEDD reduction seems to be a positive predictive factor on the duration of CAI.