Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Apomorphine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed2006

Addiction to apomorphine: a clinical case-centred discussion.

AIM: To report the case of a patient, who in the context of an anti-Parkinsonian therapy, developed addiction to apomorphine. METHODS: Clinical case description. RESULTS: Apomorphine is a dopaminergic agonist that acts directly on D2 receptors. It has been used in alcoholism, male sexual dysfunction and with diagnostic and therapeutic purposes in Parkinson's disease (PD). CONCLUSIONS: The present work describes the case of a woman with PD who developed a loss of control over the consumption of apomorphine that resulted in a significant impairment of her functioning. PD patients with high frequency develop different psychiatric symptoms. Conversely, anti-Parkinsonian drugs also generate psychiatric symptoms that can be experienced by the patient as pleasant sensations ('alerting', 'awakening', 'activating', hypomania and hypersexuality). In spite of this, addiction to these drugs in patients with PD is a very rare phenomenon. Currently, the prescription of apomorphine has been extended to patients with erectile dysfunction, which may increase the prevalence of addiction cases or of severe psychiatric symptoms.

Antiparkinson Agents↗
PubMed1991

Subcutaneous apomorphine increases regional cerebral blood flow in parkinsonian patients via peripheral mechanisms.

1. We have measured regional cerebral blood flow (rCBF) and motor function before and after the subcutaneous (s.c.) injection of apomorphine in parkinsonian patients deprived of their usual treatment for at least 48 h. 2. Nineteen patients, pretreated with domperidone (20 mg three times daily for 48 h), received a mean dose of 5.8 mg s.c. apomorphine. All patients switched 'on'. The mean motor score was significantly improved (-65%, P less than 0.01) but no significant change in rCBF was observed. 3. Seven other patients, not pretreated with domperidone, received a lower dose (0.3 mg) of s.c. apomorphine. No change in motor score was observed while the mean rCBF significantly increased (+12%, P less than 0.05). 4. We conclude that s.c. apomorphine increases rCBF in parkinsonian patients. This effect is independent of the central therapeutic effects of the drug. It is mediated by the stimulation of dopaminergic receptors of the cerebral vessels. These receptors are located outside the cerebral blood brain barrier and can be considered as 'peripheral' ones.

Aged↗
PubMed1983

Responses of pulmonary vasculature of cattle to dopamine and apomorphine.

Both dopamine and apomorphine caused concentration-dependent contractions of the bovine pulmonary artery from rest. Both of these compounds caused of the bovine pulmonary artery from rest. Both of these compounds caused relaxation of histamine-precontracted arterial and venous strips after alpha-adrenoceptor blockade. Arterial contraction elicited by dopamine was inhibited either by phentolamine (alpha-blocker) or by the dopamine-selective antagonists, spiperone and butaclamol. Apomorphine in the highest concentration (greater than 10(-5) M) inhibited dopamine-induced contractions. Dopamine- and apomorphine-induced vascular relaxations were attenuated by propranolol but not by spiperone or butaclamol. These data suggest that dopamine- and apomorphine-induced relaxation in these preparations is most likely mediated through beta-adrenergic mechanisms, whereas dopamine-induced contractions seem to involve both alpha-adrenergic and dopaminergic receptors.

Animals↗
PubMed1990

Apomorphine-induced emesis in the dog--routes of administration, efficacy and synergism by naloxone.

Apomorphine proved to be more effective as an emetic in dogs after s.c. administration than after i.m. injection with doses of 0.04 and 0.1 mg/kg. This effect is explained by an anti-emetic effect mediated by mu-receptors in the vomiting centre in the brain, which, in contrast to the chemoreceptor trigger zone, is within the blood-brain barrier. A certain delay between the stimulation of D2-receptors in the chemoreceptor trigger zone (causing emesis) and mu-receptors in the vomiting centre (producing anti-emesis) therefore results, leading to a self-limiting emesis. Blockade of the mu-receptors by naloxone increased and prolonged the effect of apomorphine. A relatively narrow range of apomorphine concentrations on s.c. administration is then effective to stimulate the chemoreceptor trigger zone, but can hardly inhibit the vomiting centre, and must therefore be considered the most suitable route for administration of apomorphine.

Animals↗
PubMed1993

Transection of corticostriatal afferents reduces amphetamine- and apomorphine-induced striatal Fos expression and turning behaviour in unilaterally 6-hydroxydopamine-lesioned rats.

Corticofugal fibres from the prefrontal, prelimbic and anterior sensorimotor cortices were transected by a wide coronal knife-cut through the forceps minor. The cut was performed on the dopamine-depleted side of unilaterally 6-hydroxydopamine-lesioned rats, or on either the right or the left side of intact rats. Sham-lesioned controls received a superficial cortical cut at the same level. Seven days after surgery, apomorphine (0.25 mg/kg s.c.) was administered to 6-hydroxydopamine-lesioned animals and D-amphetamine (5 mg/kg i.p.) was administered to the non-dopamine-denervated ones. Two hours later, the animals were perfusion-fixed for the immunohistochemical detection of the nuclear protein Fos. A computerized image analysis technique was used to quantify, bilaterally, striatal Fos expression in 11 areas of the striatum. The frontocortical transection reduced both apomorphine- and amphetamine-induced Fos expression by 33-66% within the ipsilateral caudate-putamen. The effect was observed throughout the rostral portion of the striatal complex, where the lesioned cortical fibres terminate most densely. A separate batch of unilaterally 6-hydroxydopamine-lesioned rats were used to test the effect of frontocortical transection on amphetamine- and apomorphine-induced turning behaviour. Two groups of rats, showing similar rates of contralateral turning (7-8 turns/min) in response to apomorphine (0.25 mg/kg s.c.), were subjected to either a complete frontocortical transection or a sham lesion on the dopamine-denervated side. An additional two groups, showing comparable rates of ipsilateral turning (15 turns/min) in response to amphetamine (5 mg/kg i.p.), received similar lesions, but now on the side ipsilateral to the intact dopaminergic innervation.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1990

Apomorphine does not alter amphetamine-induced dopamine release measured in striatal dialysates.

Amphetamine facilitates the release of dopamine from nerve terminals, but the mechanisms underlying this effect have not been fully delineated. The present experiments were designed to test the extent to which amphetamine-induced dopamine release is dependent on impulse flow and autoreceptor function in dopaminergic neurons. Rats were pretreated with a low dose of apomorphine (0.05 mg/kg) to inhibit dopamine neuronal activity, and the striatal dopaminergic response to amphetamine (0.5 mg/kg) was assessed by in vivo dialysis in freely moving animals. Consistent with previous results, apomorphine alone substantially decreased, whereas amphetamine increased, striatal dialysate dopamine concentrations. However, whereas apomorphine pretreatment decreased the locomotor response to amphetamine, the amphetamine-induced increase in dialysate dopamine was unaffected. These results indicate that amphetamine-facilitated dopamine release is independent of neuronal firing and autoreceptor regulation, consistent with the putative accelerative exchange-diffusion mechanism of amphetamine-induced dopamine release. Other possible mechanisms underlying the inhibitory effects of apomorphine on amphetamine locomotor activation are discussed.

Amphetamine↗
PubMed1993

The ontogeny of apomorphine-induced alterations of neostriatal dopamine release: effects on spontaneous release.

The effects of apomorphine (0.05, 0.1, and 1.0 mg/kg, s.c.) on the extracellular levels of dopamine and the dopamine metabolite 3,4-dihydroxyphenylacetic acid were studied through the use of in vivo microdialysis in the neostriatum of developing and adult rats. Fifteen-minute samples were collected from urethane-anesthetized rats 5, 10-11, 21-22, and 35-36 days old and adults and quantified by HPLC with electrochemical detection. Apomorphine attenuated extracellular levels of dopamine in all age groups, suggesting that the dopamine autoreceptor modulating release in the neostriatum is functional by 5 days of age. A dose-response effect of apomorphine on extracellular dopamine was observed in all age groups except at 10-11 days of age. Extracellular levels of 3,4-dihydroxyphenylacetic acid were also significantly decreased in all age groups, consistent with the hypothesis that synthesis-modulating dopamine autoreceptors in the neostriatum are functional by 5 days of age. Apomorphine had a significantly greater effect on extracellular 3,4-dihydroxyphenylacetic acid levels at the 0.05 and 0.1 mg/kg doses in the 5- and 10-11-day-old age groups compared with the other ages. Absolute levels of extracellular dopamine were significantly attenuated at 5 days of age compared with the other ages, and absolute levels of extracellular 3,4-dihydroxyphenylacetic acid monotonically increased with age.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Dopamine agonists in Parkinson's disease: a look at apomorphine.

Apomorphine is a D1 and D2 dopamine receptor agonist with anti-parkinsonian properties qualitatively similar to those seen with L-dopa. It was first used in the treatment of Parkinson's disease by Schwab in the 1950s but owing to its short duration of action, the need for parenteral administration, and adverse reactions including nausea, vomiting, postural hypotension and sedation, it was not widely prescribed. In the early 1970s, Cotzias confirmed its potent anti-parkinsonian effects and that some of its secondary effects were diametrically opposite to those seen with L-dopa. The advent of peripheral dopamine receptor antagonist drugs, which counteract the unwanted effects of apomorphine, and the development of new drug delivery systems including insulin pens and ambulatory mini pumps have led to the resurrection of apomorphine for the treatment of Parkinson's disease. Over the last five years in Europe, the drug has proved to be a major advance in the treatment of refractory "on-off" oscillations in Parkinson's disease. It has also been used as a diagnostic test for dopaminergic responsiveness in Parkinson syndromes and tremors of uncertain aetiology. The drug has also proved particularly useful in dealing with certain "off-period" disabilities, including pain, bladder dysfunction, dystonia and gastro-intestinal symptoms. Continuous steady state infusion of apomorphine by mini-pump may reduce the severity of "on" phase dyskinesias over time. The drug has also proved useful in the clinical pharmacological investigation of the pathophysiology of the motor response to dopaminergic drugs in Parkinson's disease and the occurrence of involuntary movement sequences. Neuropsychiatric side-effects are relatively infrequent when compared with ergolene dopamine agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Apomorphine↗
PubMed1988

Effects of DA-1- and DA-2-dopamine antagonists on apomorphine-induced inhibition of peripheral sympathetic neurotransmission.

1. Apomorphine, a dopamine receptor agonist, caused a dose-dependent inhibition of the electrically induced increase in diastolic blood pressure in the pithed rat. The anti-apomorphine effects of a range of dopamine antagonists with different DA-1/DA-2 selectivities were evaluated to characterize the dopamine receptor subtype(s) involved in this response. 2. Selective DA-2 antagonists domperidone and (-)-sulpiride and combined DA-2/DA-1 antagonists haloperidol, fluphenazine and (+)-sulpiride were active in this model, whereas the DA-1 antagonist SCH 23390 and the alpha-2 adrenoceptor antagonist idazoxan (RX-781094) were inactive. The rank order of potency of the dopamine antagonists was domperidone greater than fluphenazine greater than or equal to (-)-sulpiride greater than or equal to haloperidol greater than (+)-sulpiride much greater than SCH 23390. (-)-Sulpiride was about 25 times more potent than the (+)-isomer. 3. The observed antagonist profile suggests that the apomorphine-induced inhibition of neurogenic vasoconstriction in the pithed rat is mediated via dopamine receptors of the DA-2 subtype. The sympatho-inhibitory dopamine receptors in the cat heart have similar pharmacological characteristics. 4. The dopamine antagonists were devoid of influences on the vasoconstrictor response to electrical stimulation in the absence of apomorphine, whereas idazoxan potentiated it. This provides evidence against the participation of dopamine receptors in the modulation of the vasoconstrictor response to sympathetic stimulation in the pithed rat model.

Animals↗
PubMed1974

Apomorphine-induced and pilocarpine-induced hypothermia in mice: drug interactions and changes in drug sensitivity after caudate nucleus lesions.

1 Apomorphine and pilocarpine each produced dose-dependent hypothermic effects in mice. However, the dose-response curve for pilocarpine was steeper than that for apomorphine.2 Bilateral lesions of the caudate nucleus produced a permanent decrease in sensitivity to apomorphine but had no effect on sensitivity to pilocarpine.3 Apomorphine and pilocarpine had synergistic effects; i.e. the hypothermic effect was greater following a combination of the drugs than following either drug alone.4 The effect of apomorphine was antagonized by either haloperidol or scopolamine; only scopolamine antagonized the effect of pilocarpine.5 These results suggest that a mechanism involving dopaminergic neurones in the caudate nucleus has a modulatory role in temperature regulation.

Animals↗
PubMed1976

Stimulant properties of bromocriptine on central dopamine receptors in comparison to apomorphine, (+)-amphetamine and L-DOPA.

1. The activity of bromocriptine has been investigated in tests for the stimulation of central dopaminergic mechanisms. The results obtained have been compared with those of apomorphine, (+)-amphetamine and L-DOPA. 2. Bromocriptine (2.5 to 10 mg/kg) induced stereotyped sniffing and licking in rats. The stereotypy was more intense than that induced by L-DOPA and less intense than that of apomorphine and (+)-amphetamine over the dose ranges studied. 3. In rats lesioned unilaterally in the substantia nigra by local injection of 6-hydroxydopamine, bromocriptine, like apomorphine and L-DOPA, induced turning contralateral to the side of the lesion. The smallest dose of bromocriptine to induce turning was 0.5 mg/kg. 4. Reserpine-induced catalepsy in mice was antagonized by bromocriptine, with an ED50 of 1.8 mg/kg. It was intermediate in potency to apomorphine and L-DOPA. 5. Spontaneous locomotor activity in mice was stimulated by bromocriptine in a dose-dependent manner from 2.5 to 10 mg/kg after an initial suppression of activity. 6. In all experiments, bromocriptine was characterized by a prolonged duration of activity after a delay in the onset of effect. 7. The stereotyped behaviour induced by bromocriptine was inhibited by prior administration of pimozide, reserpine or alpha-methyl-p-tyrosine. 8. Bromocriptine-induced turning behaviour was abolished by pretreatment with pimozide, and reduced after alpha-methyl-p-tyrosine treatment. 9. The results obtained support the conclusion that bromocriptine acts by stimulating dopamine receptors in the central nervous system and that intact catecholamine synthesis and granular amine storage mechanisms are necessary for it to bring about its effects.

Amphetamine↗
PubMed1978

Hypotension produced by intravenous apomorphine in the anaesthetized dog is not centrally mediated.

1 Intravenous administration of apomorphine (1.25 to 20 microgram/kg) in the anaesthetized dog produced a dose-dependent decrease in blood pressure which was antagonized by haloperidol but not influenced by propranolol or atropine. 2 Intracarotid administration of apomorphine produced a systemic hypotension which was significantly smaller than that seen with intravenous injection. 3 Doses of apomorphine that caused a decrease in blood pressure on intravenous injection, had no effect on blood pressure or caused retching accompanied by an increase in blood pressure on intravertebral or intracisternal administration. The animals showed a marked hypotension on intravertebral or intracisternal injection of clonidine. 4 From these results it is concluded that the hypotension seen with intravenous apomorphine cannot be explained by a central site of action.

Animals↗
PubMed1981

Inhibition by apomorphine of the potassium-evoked release of [3H]-gamma-aminobutyric acid from the rat substantia nigra in vitro.

1 The spontaneous and potassium-evoked release of tritium from the rat substantia nigra prelabelled with [(3)H]-gamma-aminobutyric acid [(3)H]-GABA were assessed in vitro under conditions of superfusion.2 Kainic acid lesions performed in the right caudate nucleus resulted in a 70% reduction in the ability of the homolateral nigral cells to take up and retain [(3)H]-GABA when compared with the unlesioned side. The potassium-evoked release of [(3)H]-GABA remained proportional to the radioactivity retained in the tissue suggesting that the nigral GABA neurones that survived kainic acid treatment were still functional.3 The spontaneous outflow of [(3)H]-GABA was significantly increased by exposure to different concentrations of exogenous GABA (10 to 1000 muM) when amino-oxyacetic acid was present in the incubation medium.4 Apomorphine in concentrations ranging from 1 to 30 muM inhibited the calcium-dependent release of [(3)H]-GABA induced by 1 min exposure to 30 mM K(+). These concentrations of apomorphine did not affect the spontaneous outflow of radioactivity. In vivo administration of haloperidol 0.2 mg/kg antagonized the in vitro inhibition by apomorphine of the K(+)-evoked release of [(3)H]-GABA.5 The results obtained with apomorphine and haloperidol suggest the presence of presynaptic dopamine-like inhibitory receptors in gabaergic nerve terminals.6 Dopamine in concentrations ranging up to 300 muM did not modify either the spontaneous or the K(+)-evoked release of [(3)H]-GABA from the substantia nigra. These concentrations of dopamine effectively displaced [(3)H]-dopamine recently taken up into the substantia nigra.7 Our results do not support the view that dendritic release of dopamine from the substantia nigra might be involved in the physiological modulation of the spontaneous or the stimulation-evoked release of GABA.

Animals↗
PubMed1987

The effect of apomorphine on exocytosis and metabolic burst of polymorphonuclear leukocytes.

1 In rabbit polymorphonuclear leukocytes (PMNLs) apomorphine at 10-100 microM inhibits fMet-Leu-Phe and A23187-induced exocytosis, and the phorbol myristate acetate- and fMet-Leu-Phe-induced activation of the metabolic burst. The secretory response was not restored by washing the cells after pretreatment with apomorphine. 2 The inhibitory effect of apomorphine was not prevented by the dopamine receptor antagonists haloperidol and pimozide, nor did dopamine itself inhibit fMet-Leu-Phe-induced exocytosis. It therefore seems unlikely that effects are mediated via dopamine receptors. However, sulphydryl reagents reduced the inhibitory effect of apomorphine, suggesting that it may depend upon interaction with susceptible sulphydryl groups, the intactness of which is required for exocytosis and other functions of PMNLs.

Adenosine Triphosphate↗
PubMed1989

Interactions of drugs acting on central dopamine receptors and cholinoceptors on yawning responses in the rat induced by apomorphine, bromocriptine or physostigmine.

1. Yawning was induced by subcutaneous (s.c.) injection of low doses of apomorphine to rats. This effect decreased with increasing doses of the drug. 2. Intraperitoneal (i.p.) pretreatment of animals with sulpiride (D2-receptor blocker) reduced the frequency of the yawns induced by apomorphine, while SCH 23390 (D1-receptor blocker, s.c.) pretreatment increased the small number of yawns which was induced by higher doses of apomorphine. Administration of SCH 23390 alone to rats also produced a low degree of yawning. 3. Apomorphine-induced yawning was decreased in animals treated with SK&F 38393 (D1-agonist, i.p.), atropine (i.p.) or theophylline (i.p.). 4. Intraperitoneal injection of bromocriptine (D2-agonist) in rats also induced dose-dependent yawning. The effect was decreased in animals pretreated with sulpiride, while SCH 23390 pretreatment did not change bromocriptine-induced yawning significantly. Pretreatment of animals with SK&F 38393, atropine or theophylline reduced the number of yawns induced by bromocriptine. 5. Physostigmine (i.p.) but not neostigmine (i.p.) also induced yawning. The effect was antagonized by atropine or theophylline but not by sulpiride. Administration of SK&F 38393 decreased yawning induced by physostigmine. This inhibitory influence of SK&F 38393 was reduced by SCH 23390 in pretreated animals. Treatment of animals with SCH 23390 or bromocriptine increased the frequency of yawns induced by physostigmine. 6. It is concluded that D2-receptor activation elicits yawning through influence on cholinergic mechanisms, whereas D1-receptor stimulation decreases yawning behaviour by a negative influence on the cholinergic system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1982

Interaction of apomorphine and amantadine with ethanol in men.

Male moderate drinkers (n = 12) drank ethanol (0.8 g/kg) and then ingested one of the following: apomorphine (5 mg), amantadine (200 mg), or placebo. Subjects were tested on a battery of physiological and behavioral measures using a double-blind, within-subjects, crossover design. Postethanol ingestion of apomorphine significantly increased ethanol's effect on 3 out of the 8 measures employed (divided attention, objective and subjective inebriation ratings) without significantly altering blood ethanol concentrations or the rate of blood ethanol decline. There was no indication that apomorphine antagonized ethanol's effects. In contrast to reports indicating that amantadine antagonized ethanol depression in rodents, amantadine did not significantly alter the degree of ethanol intoxication in humans. The increase in intoxication induced by apomorphine supports suggestions that dopaminergic systems may be involved in mediating ethanol intoxication and that the sobering effect of catecholamine-augmenting drugs results from noradrenergic, rather than combined noradrenergic and dopaminergic, stimulation. Further studies are necessary to elucidate the role of pre- and postsynaptic dopaminergic receptors in mediating these effects.

Adult↗
PubMed1981

Effect of apomorphine on peripheral venous gastrin and insulin levels in conscious dogs.

Apomorphine 0.001, 0.005, 0.05 and 0.1 mg/kg were given i.v. to conscious dogs and gastrin and insulin levels were measured in peripheral venous blood. The lowest dose of apomorphine (0.01 mg/kg) did not change gastrin levels but some times caused a decrease of insulin levels, whereas the higher doses (0.005-0.1 mg/kg) induced a dose dependent increase of both hormone levels. The peak shaped release responses appeared within a few minutes and the basal values were reached again within 20 to 30 min. Apomorphine within the dose range which induced a response of insulin and gastrin also caused nausea and vomiting. After pretreatment with haloperidol (0.1 mg/kg) no signs of sickness were observed and the response of gastrin to 0.01 and 0.05 mg/kg of apomorphine was almost completely blocked, whereas the insulin response to both these dose was inhibited to approximately 50%. We conclude that the release of gastrin and insulin can be activated by stimulation of dopaminergic receptors, the anatomical location of which is not clear. Possible sites for the dopaminergic receptors are the hypothalamic region or the vagal centres in the medulla oblongata.

Animals↗
PubMed1985

Rotational behaviour elicited by intracerebral injections of apomorphine and pergolide in 6-hydroxy-dopamine-lesioned rats. II: The striatum of the rat is heterogeneously organized for rotational behaviour.

The present study compares the role of the nucleus accumbens and the striatum, as well as various regions of the striatum, in the ability of intracerebral injections of the dopamine agonists apomorphine and pergolide to elicit rotational behaviour in 6-hydroxy-dopamine-lesioned rats. We found that apomorphine and pergolide elicit rotational behaviour when injected into the denervated striatum, but not when injected into the ipsilateral nucleus accumbens. The striatum seems heterogeneously organized as regards rotational behaviour since maximal-apomorphine rotation was elicited from the corpus of the striatum as compared to the effects produced by injections into the head and the tail of the striatum. This topographical distribution is similar to the distribution of dopamine-stimulated cyclic AMP. The pergolide response is more evenly distributed in the striatum. It is suggested that the difference in the topographical distribution of the ability of apomorphine and pergolide to elicit rotational behaviour reflects a regional distribution of dopamine receptors in the striatum of the rat.

Animals↗