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PubMed1977

Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei.

Changes in stereotyped sniffing, biting and hyperactivity induced by apomorphine and D-amphetamine in the rat were determined after bilateral 6-hydroxy-dopamine (6-OHDA) lesions (8-16 micron/4micron6) of the extrapyramidal caudate-putamen (CP) (anterior and centre), globus pallidus (GP) and substantia nigra (SN), the mesolimbic nucleus (ACB), tuberculum olfactorium (TUO) and central amygdaloid nucleus (ACE). Lesions were also induced in the medial forebrain bundle in the lateral hypothalamus (LH). The 6-OHDA lesions of the CP reduced amphetamine biting but not sniffing or hyperactivity. Centrally placed 6-OHDA failed to modify any response to apomorphine but anterior locations reduced apomorphine biting. Both lesion locations led to a 45-65% reduction in striatal dopamine (DA) content, but the anterior location also involved depletions of mesolimbic DA. 6-OHDA lesions of the GP reduced striatal DA by 62% but initially potentiated before reducing both apomorphine and amphetamine biting. These lesions also potentiated amphetamine hyperactivity but other parameters were unmodified. The LH and SN lesions reduced striatal and mesolimbic DA by 75-80% and potentiated apomorphine biting. The LH lesions reduced amphetamine biting and hyperactivity but the SN lesions initially potentiated these responses. 6-OHDA lesions of the ACB reduced the DA content of this nucleus by 72% but had little effect on the TUO: these lesions reduced the duration of amphetamine hyperactivity and potentiated apomorphine biting. In contrast, equally selective lesions of the TUO (80% DA depletion) enhanced the locomotor activity response to both apomorphine and amphetamine; apomorphine biting was also increased but other parameters were unmodified. Lesions of the ACE depleted amygdaloid DA by at least 80% and reduced or abolished apomorphine and amphetamine biting in the chronic stage. The results indicate that the sites for mediation of sterotyped sniffing, biting or hyperactivity are not the same for apomorphine and amphetamine, and that each behavioural state involves the functioning of more than one DA-containing area.

Amygdala↗
PubMedDate not supplied

Penfluridol blockade of apomorphine: dependence of duration on species and endpoint.

Penfluridol, at relatively low doses, blocks apomorphine-elicited emesis in dogs and apomorphine-elicited floor pecking in pigeons for over a month. In mice tested for apomorphine-elicited hypothermia, and in rats tested for apomorphine-elicited chewing behavior, however, the anti-apomorphine activity of penfluridol does not persist for longer than 2-3 days even when high doses of penfluridol are given. In rabbits tested for apomorphine-induced hyperthermia and gnawing, on the other hand, penfluridol blocks apomorphine for about a week. Thus, of the 5 species tested, only in rabbits does the duration of penfluridol's anti-apomorphine action approximate the 1-week duration reported from human therapeutic trials. In mice given high-dose penfluridol apomorphine consistently elevates body temperatures, rather than exerts its usual hypothermic response. Conversely, in rabbits given penfluridol apomorphine tends slightly to decrease body temperatures, rather than exert its usual hyperthermic response.

Animals↗
PubMed1983

Stereoisomers of apomorphine differ in affinity and intrinsic activity at presynaptic dopamine receptors modulating [3H]dopamine and [3H]acetylcholine release in slices of cat caudate.

We investigated the effects of R(-)-apomorphine and S(+)-apomorphine on dopamine receptors modulating electrically evoked [3H]dopamine and [3H]acetylcholine release from slices of cat caudate nucleus. R(-)-Apomorphine inhibited the release of both [3H]dopamine and [3H]acetylcholine with an IC50 of 20 nM, while S(+)-apomorphine was without inhibitory action on the electrically evoked release of either neurotransmitter at concentrations up to 1 microM. At a concentration of 1 microM, however, S(+)-apomorphine antagonized the inhibition by R(-)-apomorphine, producing a parallel five-fold shift to the right in the concentration-response curve to R(-)-apomorphine. These results indicate that S(+)-apomorphine is devoid of intrinsic activity to stimulate presynaptic dopamine receptors modulating the electrically evoked release of dopamine and acetylcholine. In addition, S(+)-apomorphine has an approximately ten-fold lower affinity for presynaptic dopamine receptors compared to R(-)-apomorphine.

Acetylcholine↗
PubMed1980

Effects of apomorphine on escape performance and activity in developing rat pups treated with 6-hydroxydopamine (6-OHDA).

The effects of apomorphine and excape learning were examined in normal developing rat pups and littermates preferentially depleted of brain dopamine by the intracisternal administration of 6-hydroxydopamine (6-OHDA) at 5 days of age, a treatment which resulted in a rapid and permanent reduction in brain dopamine to concentrations 12-29% of littermate controls while norepinephrine was not significantly altered. At 19 days of age both 0.1 and 1.0 mg/kg doses of apomorphine increased general motor activity in normal but not 6-OHDA treated pups (though these pups were significantly hyperactive prior to apomorphine). At 26 days only the 1.0 mg/kg dose increased motor activity in both normal and 6-OHDA pups. Exploratory activity at 30 days in both normal and 6-OHDA pups was first reduced then abolished by progressive doses of apomorphine. Stereotyped activity was increased by 0.1 and 1.0 mg/kg apomorphine at 19 days in both normal and 6-OHDA pups. By 26 days, apomorphine no longer produced intense sterotypies in normal pups, but did effect such responses in 6-OHDA treated animals. Administration of apomorphine resulted in a disruption of escape performance in a T-maze and shuttle box in normal pups only at 1.0 mg/kg but disrupted performance in 6-OHDA treated animals at both 0.1 and 1.0 mg/kg dosages. These results indicate a peak effect of apomorphine on general motor activity at three weeks of age in normal pups. Our results also suggest that apomorphine will disrupt escape learning, effects that appear to be correlated with the apomorphine induced increase in motor activity.

Animals↗
PubMed1986

Effects of pretreatment with naloxone on behaviours induced by a small dose of apomorphine.

The opiate antagonist, naloxone, was used to determine whether endogenous opioids modulate behavioural effects induced by a low dose of apomorphine. Before administering apomorphine (0.075 mg/kg) or saline, rats were pretreated with naloxone (1 mg/kg) or saline. Each subject received all 4 possible treatments (saline-saline, saline-apomorphine, naloxone-saline, and naloxone-apomorphine) in random order. Naloxone reduced the frequency and altered the timing of apomorphine-induced yawning, reduced the frequency of apomorphine-induced stretching, potentiated the effect of apomorphine on delaying grooming of the body, and did not affect the hypoactivity induced by apomorphine. Moreover, like apomorphine, naloxone itself reduced activity. Furthermore, naloxone and apomorphine injected together increased the latency to groom the face. These results suggest that in some circuits, endogenous opioids interact with dopaminergic autoregulatory mechanisms.

Animals↗
PubMed1991

Apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity in mice.

Effects of the dopamine (DA) D1 antagonist SCH 23390 and the DA D2 antagonist (-)-sulpiride on apomorphine-induced characteristic changes in spontaneous motor activity were investigated in mice using the system we have devised for automatically analyzing animal behaviors in mice. Apomorphine (3 mg/kg, SC) markedly increased parameters of spontaneous motor activity such as locomotor activity and rearing time. Apomorphine-induced increase in locomotor activity had peaks at 5-20 and 30-50 min after administration, and its trough was closely related to the marked increase in rearing time induced by this agonist. Apomorphine-induced locomotor activity accumulated over a 40-min period from 5 to 45 min after apomorphine injection, during which apomorphine-induced increase in rearing time peaked, was significantly increased by intraperitoneal administration of 0.03 and 0.1 but not 0.01 mg/kg SCH 23390. Apomorphine-induced increase in rearing time was dose-dependently depressed by this antagonist. In contrast, (-)-sulpiride (10-40 mg/kg, IP) decreased apomorphine-induced increases in rearing time and locomotor activity rather than enhancing the latter parameter. These data suggest that the apparent enhancement by SCH 23390 of apomorphine-induced locomotor activity is mediated through DA D1 receptors and does not always correlate with depression of apomorphine-induced rearing behavior in mice.

Animals↗
PubMed1992

Inhibition of nigral dopamine neurons by systemic and local apomorphine: possible contribution of dendritic autoreceptors.

Peripheral administration of low doses of dopamine agonist apomorphine induces a strong and short-latency inhibition of dopamine neurons in the substantia nigra, presumably via the activation of somatodendritic autoreceptors. We studied the site of action of apomorphine in anesthetized rats using volume-controlled pressure microejection combined with single unit recordings. Microapplication of apomorphine in the immediate vicinity of nigral dopamine neurons did not mimic the effect of intravenous administration of apomorphine (50 micrograms/kg), regardless of the concentration or volume used (10(-10)-10(-2) M, 10-100 nl). In contrast, the inhibition produced by systemic apomorphine was mimicked by drug application at a site 300 microns lateral and 600 microns ventral from the recording site in the zona reticulata of the substantia nigra, a region rich in dendrites of dopamine neurons. The inhibition induced by such a distant application of apomorphine could be reversed by systemic injection of D2, but not D1, receptor antagonists. Non-dopaminergic substances such as GABA, bicuculline or lidocaine were more effective when ejected close to rather than distant from the recording site, in a manner opposite to that of apomorphine. Similar to apomorphine, dopamine and D2 receptor agonists were more potent when intranigral applications were made at sites distant from, rather than close to, the recorded dopamine cells. Ejection of D2 antagonists in the substantia nigra zona reticulata attenuated the inhibitory effect of subsequent systemic apomorphine. Our results, together with other previous studies on the location of D2 receptors on dopamine neurons, suggest that peripheral administration of low doses of apomorphine inhibits nigral dopamine neurons by acting at D2 receptors located on the dendrites of these neurons.

Animals↗
PubMed2005

A review of intermittent subcutaneous apomorphine injections for the rescue management of motor fluctuations associated with advanced Parkinson's disease.

BACKGROUND: As Parkinson's disease (PD) progresses,despite optimized pharmacotherapy, patients experience more frequent fluctuations between symptomatic improvement ("on" times) and the return of motor features ("off" times). Apomorphine, the first injectable dopamine agonist available in the United States, is indicated for the acute treatment of "off" episodes (eg, end-of-dose wearing-off episodes, unpredictable "on/off" episodes) in patients with advanced PD who are receiving medically optimal antiparkinsonian therapy. OBJECTIVE: This article reviews the pharmacology,clinical efficacy, and tolerability of intermittent subcutaneous apomorphine injections for the management of "off" episodes in patients with PD. METHODS: MEDLINE (1966-July 2005), the Cochrane Database of Systematic Reviews, and International Pharmaceutical Abstracts (1970-July 2005) were searched for original research and review articles published in English. The search terms were apomorphine and Parkinson's disease. The reference lists of articles were also consulted, as was selected information provided by the manufacturer of apomorphine. All relevant identified studies on intermittent subcutaneous administration of apomorphine were included in the review; trials of continuous subcutaneous infusion and non-subcutaneous administration of apomorphine were excluded. RESULTS: Intermittent subcutaneous administration of apomorphine produced consistent rescue from "of" episodes in patients with advanced PD, with a symptomatic motor improvement between the predose "off" state and postdose "on" state similar to that achieved with levodopa. The onset of effect occurred within 20 minutes, and the duration of effect was approximately 100 minutes. The therapeutic rescue dose ranged from 2 to 6 mg. During the clinical development program for subcutaneously injected apomorphine, patients required a mean of approximately 3 rescue doses per day. Common adverse effects occurring in > or =20% of patients were injection-site reaction, yawning, dyskinesias, drowsiness, nausea and vomiting, dizziness or postural dizziness, and rhinorrhea. CONCLUSIONS: The available clinical studies indicate that apomorphine is effective in providing prompt and consistent rescue from "off" episodes in patients with PD. Antiemetic prophylaxis and close medical supervision are recommended when initiating apomorphine therapy.

Antiparkinson Agents↗
PubMed2004

Alfuzosin improves penile erection triggered by apomorphine in spontaneous hypertensive rats.

OBJECTIVES: Growing evidence suggest that BPH is a risk factor for ED. Since alfuzosin is a cornerstone in the treatment of BPH patients, we assessed the effect of alfuzosin on erectile function in rats when combined with a pro-erectile drug such as apomorphine. METHODS: Potencies of alfuzosin, apomorphine or the combination to relax norepinephrine (NE) precontracted corpus cavernosum tissue of spontaneous hypertensive rats (SHR) were determined. In anaesthetized rats, intracavernous and blood pressures were recorded after administration of apomorphine (10-250microg/kg s.c.) and alfuzosin (3-30microg/kg i.v.). RESULTS: Alfuzosin fully relaxed the NE-precontracted penile tissue (pIC(50)=6.62+/-0.7) while apomorphine, up to 10microM, did not produce any relaxation. The potency of alfuzosin to relax erectile tissue was not further enhanced with 10microM apomorphine. Apomorphine induced erections in rat while alfuzosin alone did not. However, alfuzosin (30microg/kg) significantly enhanced the potency of apomorphine, to induce erections (ED(50)=25microg/kg versus 57microg/kg). In addition, alfuzosin even at 3microg/kg, significantly increased the intracavernous pressure (ICP) during erectile events up to 52-55mmHg when compared to ICP values of 29mmHg with 50microg/kg apomorphine alone. CONCLUSION: These results show that alfuzosin enhances the number and amplitude of erections induced by apomorphine in SHR. Therefore, clinical evaluation of alfuzosin in association with apomorphine is warranted.

Adrenergic alpha-Antagonists↗
PubMed2001

Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage.

(R)-apomorphine is a non-selective dopamine (DA) agonist which is used in the treatment of Parkinson's disease. In addition to symptomatic effects, apomorphine exerts a neuroprotective activity in specific experimental models. For instance, apomorphine prevents experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties, instead it appears to be grounded on the antioxidant and the free radical scavenging effects of the compound. In this study, we sought to determine whether apomorphine protects against methamphetamine toxicity. We found that apomorphine (1; 5 and 10 mg/kg) dose-dependently protects against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA loss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of striatal methamphetamine nor to hypothermia as indicated by measurement of striatal methamphetamine and body temperature at different time intervals after drug administration. The effects of apomorphine were neither opposite to, nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with haloperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons and call for further studies aimed at evaluating potential neuroprotective effects of apomorphine in Parkinson's disease.

Animals↗
PubMed1998

Drug conditioning induced by intrastriatal apomorphine administration.

The present study examined (1) whether the neostriatum is involved in a drug-induced conditioned locomotor response and; (2) whether this structure participates in the development of behavioral sensitization. Moreover, the present study addressed the question whether the development of behavioral sensitization is necessary for the induction of conditioning. Rats received injections of either apomorphine (2 microg) or vehicle (solution of 0.1% ascorbate/saline) into the dorsal neostriatum daily for 7 days. These treatments were performed immediately prior to (apomorphine-paired group and vehicle group) or 30 min following (apomorphine-unpaired group) 10-min placement in an open field which served as the test environment. After a 3-day drug withdrawal period, the animals were given a 10-min non-drug vehicle test trial in the test environment. Three days later, a drug test with apomorphine was administered to the animals of the paired and unpaired treatment groups; the vehicle group again received an injection of vehicle. The analysis of locomotor activity in the open field (measured as the distance traversed) revealed that locomotor activity in the apomorphine-paired group was higher than in the other groups. There were no indications for behavioral sensitization to intrastriatal apomorphine, since the locomotor response in the apomorphine-paired group did not increase, but rather decreased with daily repeated injections of apomorphine. Furthermore, only the apomorphine-paired animals showed a higher locomotor response when tested after an intrastriatal injection of vehicle in the previously apomorphine-paired environment, which is indicative of a conditioned drug effect. These results suggest that the neostriatum is directly involved in the development of drug-induced conditioning of locomotor behavior but not in the establishment of behavioral sensitization.

Animals↗
PubMed1997

Distribution of apomorphine enantiomers in plasma, brain tissue and striatal extracellular fluid.

Steady-state concentrations of apomorphine enantiomers were measured in the extracellular fluid collected from rat brain striatum by microdialysis. The free and total concentrations of both enantiomers were also measured in plasma as well as the total concentrations in different brain regions (striatum, cortex and cerebellum). We noticed no regional difference in the total concentrations of the two enantiomers. The extracellular concentrations were much lower, amounting to 8% for R(-)-apomorphine and 4% for S(+)-apomorphine, of the total brain tissue concentrations. The microdialysis samples contained 12 times more (R(-)-apomorphine and 5 times more S(+)-apomorphine than the free apomorphine measured in plasma. The extracellular concentrations of R(-)-apomorphine (129 +/- 20 pmol/ml) were significantly higher (P = 0.001, n = 6), than those of S(+)-apomorphine (70 +/- 10 pmol/ml). These results indicate that both enantiomers of apomorphine concentrate equally in brain cells, and that a stereoselective uptake system could operate for R(-)-apomorphine at the blood-brain barrier level.

Animals↗
PubMed1988

Latent sensitization to apomorphine following repeated low doses.

In two experiments, the effect of repeated injections of apomorphine on locomotor activity of rats was determined. In each experiment, different groups of rats were injected with either apomorphine (0.2, 1.0, or 5.0 mg/kg) or vehicle at either 24 or 72 hr intervals and tested for locomotor activity in photocell arenas. In Experiment 2, following 13 treatment sessions with various doses, all groups were first tested for activity following a 5.0 mg/kg dose of apomorphine and then given vehicle only prior to the final activity test session. Major findings were as follows: (a) repeated injections of 1.0 and 5.0 mg/kg apomorphine produced a progressively greater increase in activity with each injection (i.e., sensitization); (b) injections of 0.2 mg/kg of apomorphine produced a slight inhibition of activity, which did not change with repeated injections; (c) prior treatment with 0.2 mg/kg of apomorphine resulted in a significantly greater activity increase following a 5.0 mg/kg dose of apomorphine than did prior vehicle treatments; and (d) chronic pretreatment of rats with apomorphine did not affect their activity level following a vehicle injection. These findings suggest that sensitization to apomorphine is a graded, rather than an all or none, phenomenon dependent on the dose of apomorphine repeatedly administered. In addition, these results are inconsistent with autoreceptor tolerance and conditioning explanations of dopamine agonist-induced sensitization effects.

Animals↗
PubMed2002

A European multicentre study to evaluate the tolerability of apomorphine sublingual administered in a forced dose-escalation regimen in patients with erectile dysfunction.

OBJECTIVE: To determine the risk-benefit ratio of a forced dose-escalation regimen (2 to 3 to 4 mg) in a European clinical study evaluating apomorphine sublingual (SL) in treating erectile dysfunction (ED), by evaluating the overall tolerability and efficacy of the regimen compared with placebo in patients with ED, and evaluating efficacy by assessing the proportion of successful attempts resulting in sexual intercourse. PATIENTS AND METHODS: This randomized, double-blind, two-arm, parallel-group study was conducted in 507 patients enrolled at 34 European sites. After a 1-2 week screening period, patients were treated for 8 weeks with either placebo or apomorphine SL administered as a forced dose-escalation regimen. Heterosexual men (aged 18-70 years) were eligible for participation in the study if they were in stable health, a stable relationship of > or = 6 months duration, had a history of erectile inability, and were diagnosed with ED (successful in fewer than half of attempts to attain and maintain an erection firm enough for intercourse during the 30 days before screening). Patients provided information (recorded on diary cards and reviewed at each study visit) about the frequency and success in achieving erections and of sexual intercourse attempts during both the screening and treatment periods. The dosing regimen required patients to take one tablet of apomorphine SL (2 mg for 2 weeks, then 3 mg for 2 weeks and finally 4 mg for the remaining 4 weeks) or placebo 15-25 min before intercourse, and intercourse was to be attempted at least twice a week. Safety data were collected throughout the 8-week study period, and included recording adverse events, vital signs and changes in laboratory test values for standard haematology and biochemistry variables. The primary efficacy variable was the proportion of successful attempts, defined as an erection rigid enough for sexual intercourse, occurring after dosing (successful intercourse rate). The proportion of erections achieved was a secondary efficacy variable. RESULTS: Of the 507 patients, 254 received apomorphine SL and 253 received placebo; 87% of patients in both groups completed the 8-week treatment period. Of the patients receiving apomorphine SL, 24% had hypertension, 11% had coronary artery disease, 10% had diabetes, and 5.5% had benign prostatic hypertrophy; 62.6% of treated patients received concomitant medications for these maladies. The treatment groups were balanced for demographic and baseline variables, including comorbidity factors. Treatment-emergent adverse events, reported by > 5% of patients in the treated group, were nausea (9.8%), dizziness (7.1%) and headache (6.7%), compared with 0.4%, 2.4% and 4.0%, respectively, in the placebo group. Sixty-six patients withdrew from the study, 16 because of study drug-related adverse events (12 from the apomorphine and four from the placebo group). Six patients (three in each group) reported a total of nine serious treatment-emergent adverse events, all of which resolved by the end of the study. In the intention-to-treat population, the proportion of successful attempts at sexual intercourse and of erections were statistically greater in the apomorphine than in the placebo group (P = 0.001 and 0.021, respectively); analysis of the per-protocol population results confirmed this significant difference. CONCLUSION: This European study supports the safety and tolerability of apomorphine SL despite the forced escalation to a 4-mg dose (exceeding the approved 2-3 mg dose). Adverse effects were not treatment-limiting. These results further support the clinically significant efficacy of apomorphine SL for treating ED at all doses used. The risk/benefit ratio supports apomorphine SL as a safe and effective alternative in managing ED.

Administration, Sublingual↗
PubMed2001

Intravenous apomorphine therapy in Parkinson's disease: clinical and pharmacokinetic observations.

Six patients with Parkinson's disease and refractory motor fluctuations, with severe subcutaneous (s.c.) nodule formation as a result of long-term s.c. apomorphine infusions, were switched to intravenous (i.v.) therapy via a long-term in-dwelling venous catheter. Five patients were followed-up for a mean of 7 months (range 0.5-18 months). All patients had plasma apomorphine concentrations measured at baseline during s.c. infusions and three had follow-up measurements when stabilized on i.v. therapy, to test the hypothesis that motor fluctuations in these patients are largely due to impaired absorption of apomorphine. The mean i.v. rate of 9.0 mg/h (range 5-14 mg) and 24-h dose of 256.7 mg (range 90-456 mg) of apomorphine were not significantly reduced compared with the s.c. route (9.24 mg/h and 243.4 mg). However, additional oral anti-parkinsonian medication was reduced by a mean of 59%, and 'off' time was virtually eliminated (mean reduction from 5.4 to 0.5 h per day, P< 0.05). There was also a significant reduction in dyskinesias and markedly improved quality of life. Pharmacokinetic analysis demonstrated more reliable and smoother delivery of apomorphine via the i.v. route, although 'off' periods were not always explained by low plasma apomorphine concentrations. Complication rates were high and included three unforeseen hazardous intravascular thrombotic complications, secondary to apomorphine crystal accumulation, necessitating cardiothoracic surgery. We conclude that i.v. apomorphine therapy holds promise as a more effective way of controlling motor fluctuations than the s.c. route. However, further preclinical research is required before i.v. Britaject apomorphine can be recommended for routine clinical practice. Even when stable plasma apomorphine concentrations were achieved, motor fluctuations could not be totally eradicated, suggesting that postsynaptic receptor changes may also play a role in the refractory 'off' periods in these patients.

Aged↗
PubMed1994

Clinical usefulness of apomorphine in movement disorders.

Apomorphine, the first dopamine agonist to be synthesized, has received a renewed interest in the last few years. This compound acts powerfully on D1 and D2 dopamine receptors and has the most complete pharmacological profile of all clinically available dopamine agonists. When given subcutaneously, apomorphine consistently reverses levodopa-resistant "off" periods in parkinsonian subjects: thus, it is used in cases with severe motor fluctuations, either by continuous infusion with a portable pump or by multiple injections. Studies based on this approach have been highly encouraging, as they have shown a significant reduction in off time and a good drug tolerability. The main side effect has been the occurrence of nodular skin lesions, especially when continuous infusions were used. At variance with other dopamine agonists, a low incidence of psychiatric morbidity has been reported with apomorphine. The few available comparative reports have shown that this compound is more potent and better tolerated than lisuride. Parenteral apomorphine has been used in Parkinson's disease (PD) to replace levodopa after surgery or to treat the malignant syndrome brought about by sudden levodopa withdrawal. Acute challenge with apomorphine has been used to test dopaminergic responsiveness in parkinsonian syndromes and in dystonia. The clinical response to apomorphine may predict the effect of a chronic therapy with levodopa in approximately 90% of PD cases. Further studies are still necessary to evaluate the exact relationship between the acute response to apomorphine and a chronic therapy. In addition, apomorphine has been used to conduct clinical pharmacological studies in PD, for it is particularly well suited for research on the pharmacodynamics of central dopamine receptors. In summary, apomorphine appears to be an efficacious and safe drug for the treatment of advanced PD. It must still be considered under clinical evaluation as a test drug for acute challenge in PD and dystonia. Finally, in our opinion, the available data suggest apomorphine (in conjunction with domperidone) as a first-choice treatment for the neuroleptic malignant syndrome and the temporary replacement of levodopa (e.g., after gastrointestinal surgery).

Antiparkinson Agents↗
PubMed1991

Selective effects of low doses of apomorphine on spatiotemporal contrast sensitivity in healthy volunteers: a double-blind placebo-controlled study.

1. Apomorphine (1 and 5 micrograms kg-1) and placebo were given to nine normal volunteers, using a Latin-square design and double-blind procedures. The visual perception of static and moving patterns (static and motion contrast sensitivity) was evaluated before and 15 min after the dose administration. 2. Apomorphine (1 and 5 micrograms kg-1), as compared with placebo, led to a significant overall reduction of the visual perception of movement. This effect was dose-related, and apomorphine (5 micrograms kg-1) induced a more pronounced decrease in the visual perception of movement than apomorphine (1 microgram kg-1). With apomorphine (5 micrograms kg-1), the reduction was more pronounced for low spatial frequencies, and was linearly inversely correlated to the spatial frequency for a temporal frequency of 3 Hz. Finally, no significant effect of apomorphine was observed for sensitivity to static patterns. 3. Several non exclusive hypotheses may be suggested: The effects of apomorphine may result from stimulation of retinal D1- and/or D2-dopaminergic receptors. Apomorphine may increase the surround inhibition of ganglion cells' receptive-fields. This modification of the centre-surround balance may explain the decrease in contrast sensitivity for low spatial frequencies. The specific effects of apomorphine on the visual perception of movement support the hypothesis that apomorphine preferentially affects the magnocellular pathway which mediates sensitivity to moving patterns.

Adult↗
PubMed2004

Diagnostic and therapeutic value of apomorphine in Parkinsonian patients.

Apomorphine is a dopamine agonist administered subcutaneously for the management of motor symptoms of Parkinson's disease (PD). Patients with Parkinsonian syndrome underwent an apomorphine challenge for therapeutic efficacy, a positive response being a reduction of > 15% score on motor unified PD rating scale. Of the 42 patients, aged 37-81, disease duration 12 months to 20 years, 36 had a positive response. Six non-responders were later diagnosed as non-PD as compared with only two of the 36 responders. Tremor-predominant patients obtained higher motor response. Few patients demonstrated a delayed positive response. Seven (three idiopathic PD (iPD), four non-PD) suffered adverse reactions of nausea, vomiting or ill-sustained symptomatic fall in BP. Majority of the patients who continued with apomorphine therapy were able to reduce levodopa and achieved an improvement in dyskinesia and motor symptoms. Thirteen responding patients were managed by increasing dopamine agonists. Five patients, intolerant of oral dopamine agonists, were able to beneficially tolerate apomorphine. Age and disease duration did not influence tolerability or efficacy. The patients treated with apomorphine were able to significantly reduce the dose of levodopa, and there was a reduction in dyskinesia, hallucinations and fluctuations (all p < 0.05). In some patients, apomorphine prevented admission to institutions. We also describe the use of apomorphine in acutely ill patients unable to ingest oral medication. Apomorphine seems to have a diagnostic element for iPD. Its use leads to a reduction in dyskinesia, improvement in motor symptoms and prevention of institutional care. Apomorphine test also identifies patients likely to benefit with an increase in oral medication. Age and disease duration should not prevent the use of this valuable drug. Apomorphine also has a role in acutely ill PD patients.

Acute Disease↗