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At least 595 records · Page 33Linked to original sources
PubMed2002

The effect of apomorphine on blink kinematics in subhuman primates with and without facial nerve palsy.

PURPOSE: The purpose of this study was to document the effect of acutely delivered apomorphine, a dopamine receptor agonist with both D1 and D2 properties, on blink rate and the amplitude-velocity characteristics of eyelid kinematics in a group of nonhuman primates. METHODS: Three cynomolgus and two rhesus macaques underwent baseline recordings for eyelid kinematics, using the Robinson search coil technique. Next, each animal received a 0.15-mg/kg subcutaneous injection of apomorphine. Recordings were taken at 45 and 90 minutes, respectively, after injection. Blink rates per minute were obtained, and main sequence relationships were calculated for every animal. The data were pooled for each eyelid, excluding one monkey who was affected by facial nerve palsy and was analyzed separately. RESULTS: Monkeys with normal facial musculature and normal baseline blink rates showed consistently longer, faster blinks after apomorphine. The main sequence relationship, although tending to be lower, was not statistically different from baseline. One monkey, with prior facial nerve palsy and a very steep amplitude versus peak velocity relationship, showed normalization of the main sequence slope after apomorphine at both 45 and 90 minutes after injection. CONCLUSIONS: Apomorphine consistently lowers blink rate and changed blink metrics in normal monkeys and, more dramatically, in a monkey with facial nerve palsy. These findings add credence to models in which dopamine deficiency plays a role in the modulation of blink kinematics.

Animals↗
PubMed1992

[Sublingual administration of apomorphine in the treatment of motor fluctuations in Parkinson disease].

Apomorphine, a mixed dopaminergic agonist was given sublingually to 12 patients with Parkinson's disease disabled by severe on-off fluctuations. The patient's mean age was 57 years and the duration of Parkinson's disease was 12 years. All patients were also given domperidone (60 mg/day). Apomorphine was administered as soon as the off periods appeared. On periods were observed in 11 patients, with a mean apomorphine dose of 40 mg for each administration (extremes values: 20-60 mg). One patient had no motor benefit after an apomorphine dose of 120 mg. The mean duration of daily off periods was reduced by 64 per cent in 11 patients, for a mean duration of 8 months (extremes values: 2-12 months). Four patients developed stomatitis or gingival edema and stopped treatment. This pilot study shows that sublingual apomorphine, during a mean period of 8 months, significantly decreases off periods in parkinsonian patients. Others studies are necessary to confirm these results.

Administration, Sublingual↗
PubMed1992

Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: site of action in the brain.

The effect of morphine administered systemically or into the paraventricular nucleus of the hypothalamus (PVN) on penile erection and yawning induced either by oxytocin or by the dopaminergic agonist apomorphine was studied in male rats. Systemic morphine (0.5 to 5 mg/kg intraperitoneally [IP]) prevented in a dose-dependent manner penile erection and yawning induced by the intracerebroventricular injection (ICV) of oxytocin (30 ng) or by the subcutaneous (SC) administration of apomorphine (80 micrograms/kg). Morphine (0.1 to 5 micrograms), but not U-69,593 (5 micrograms), injected into the PVN 10 minutes before oxytocin or apomorphine, was found to be able to prevent penile erection and yawning induced by the unilateral PVN microinjection of oxytocin (10 ng) or apomorphine (50 ng). The morphine-induced prevention of these behavioral responses was abolished by pretreatment with naloxone (3 mg/kg IP) 15 minutes before morphine. The present results suggest that morphine prevents apomorphine- and oxytocin-induced penile erection and yawning by inhibiting the activity of oxytocinergic neurons through mu-type receptors in this hypothalamic nucleus.

Analgesics↗
PubMed1991

Apomorphine--test in dystonia.

In a doubleblind, placebocontrolled design subcutaneous apomorphine was given to 7 patients with dystonic movement disorders to assess dopamine sensitivity of their symptoms. Five patients who displayed a marked clinical improvement after the apomorphine test injections subsequently responded to oral or continuous dopaminergic therapy. The effective apomorphine doses correlated with the doses of dopaminergic drugs. Two non-responders to apomorphine did not benefit from dopaminergic therapy. Apomorphine application thus seems to be a valuable test predicting dopamine sensitivity in dystonia.

Apomorphine↗
PubMed1991

The effect of apomorphine on operant behavior in rats under normoxic and hypoxic conditions.

We studied the effect of apomorphine on the performance of rats, maintained on a free-operant shock-avoidance schedule under normoxic and hypoxic (12, 10, and 8% O2) environments. In a normoxic environment, apomorphine (1, 2, 4, and 8 mg/kg, i.p.) produced stereotyped behaviors and dose-dependent increases in the rats' lever-pressing response rate. In a hypoxic environment, however, the increase of the response rate induced by apomorphine at 1 mg/kg was suppressed by the hypoxic conditions tested. At a dose of 8 mg/kg apomorphine, it was also suppressed by exposure to severe hypoxia (10 and 8% O2). These results suggest that the impairment of avoidance behavior in rats by hypoxia was not always improved by apomorphine, and that the degree of improvement depends on the combined effects of the dosage of the drug injected, the degree of hypoxia, and the type of behavior observed.

Animals↗
PubMed1991

Nicardipine protects against chronic ethanol- or haloperidol-induced supersensitivity to apomorphine-induced aggression.

Affective apomorphine-induced aggression was induced in originally nonaggressive rats after withdrawal from prolonged ethanol or haloperidol treatment. If the animals were co-administered Ca(2+)-channel blockers like diltiazem or verapamil the aggressive response to apomorphine was markedly decreased. Nicardipine (2 and 5 mg/kg b.i.d.) significantly attenuated the aggression-enhancing effect of chronic ethanol or haloperidol withdrawal in nonaggressive rats. Chronic nicardipine, alone, did not enhance aggressive behavior in the nonaggressive rats. Acutely, it suppressed apomorphine-induced aggression but did not alter open field activity when injected into aggressive rats. These results demonstrate that a Ca(2+)-channel blocker of the dihydropyridine type can prevent the development of an ethanol or haloperidol-withdrawal supersensitivity to apomorphine-induced aggression. It attenuates the aggression-inducing effect of apomorphine without impairing general activity.

Aggression↗
PubMed1978

Apomorphine stereotypies and transmitter mechanisms in the striatum. II. Interactions between GABA-ergic and cholinergic transmission.

The interactions between the GABA-ergic and cholinergic transmissions in the striatum of male mice are determined through microinjection in the striatum of agents influencing these types of transmission in cases of apomorphine stereotypies. It is found that the agents acting on the cholinergic transmission (agonists and antagonists of the muscarinic and nicotinic cholinoreceptors), antagonize considerably the reducing effect on apomorphine stereotypies of the agents acting on GABA-ergic transmission. Conversely, the agents acting on GABA-ergic transmission (pre- and post-synaptic) intensify or weaken the effects of the agents acting on the cholinergic transmission with respect to apomorphine stereotypies, though the difference is not entirely significant. The influence of the effects of the agents acting on the GABA-ergic transmission in cases of apomorphine stereotypies is thought to be due to the antagonistic action of the striatal cholinergic neurones on the GABA-ergic neurones, while the latter interact with the striatal dopaminergic neurones either directly or through the mediation of substantia nigra. The lack of direct interactions between the GABA-ergic and the cholinergic neurones in the striatum explains the weak influence on cholinergic transmission exerted by the agents acting on the GABA-ergic transmission with respect to apomorphine stereotypies.

Animals↗
PubMed1987

Dopamine D1 and D2 receptors are sensitive to the cationic form of apomorphine.

The protonated form of apomorphine was found to be active at the high affinity state of dopamine D1 and D2 receptors in canine striatum, since pH reduction from 7.4 to 6.4 enhanced the apomorphine potency 3-fold at both these sites without affecting the potency of the permanently charged apomorphine methiodide. It was estimated that the protonated form of apomorphine was approximately 20-fold more potent than the uncharged form of apomorphine at both the D1 and the D2 receptors.

Animals↗
PubMed1985

Presynaptic inhibitory dopamine receptors on noradrenergic nerve terminals: analysis of biphasic actions of dopamine and apomorphine on the release of endogenous norepinephrine in rat hypothalamic slices.

Electrical field stimulation (5 Hz)- or high K+ (20 mM)-evoked release of endogenous norepinephrine from superfused rat hypothalamic slices in the presence of cocaine (20 microM) was measured by high-performance liquid chromatography with an electrochemical detector. Apomorphine (10-1000 nM) dose-dependently facilitated the electrically evoked release. Apomorphine (1 microM)-induced facilitation was abolished by pretreatment with yohimbine (100 nM), was converted to inhibition by yohimbine (1 microM), but was not antagonized by propranolol (300 nM). Epinephrine (100 nM) decreased the electrically evoked release and the decrease was antagonized by yohimbine (100 nM) and by apomorphine (100 nM), but not by S-sulpiride (100 nM). In the presence of yohimbine (1 microM), apomorphine (10-1000 nM) dose-dependently inhibited the electrically evoked release. Furthermore, in the presence of tetrodotoxin (300 nM), apomorphine (100 nM) also decreased the high K+-evoked release and this decrease was antagonized by S-sulpiride (100 nM). Dopamine produced biphasic actions on the electrically evoked release, a dose-dependent decrease at 30 and 100 nM and an increase at 300 and 1000 nM. Dopamine (300 nM)-induced increase was antagonized by propranolol (300 nM) but not by yohimbine (100 nM). The dopamine (100 nM)-induced decrease was antagonized by S-sulpiride (1 nM), but not by the R-isomer. S-sulpiride (10 to 100 nM) alone dose-dependently increased the electrically evoked release, whereas the R-isomer had no effect. Haloperidol (100 nM) also increased the electrically evoked release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Various physiological characteristics of primary radiation reaction and its apomorphine model].

Experiments were performed on 52 dogs exposed to irradiation at a dose of 5-80 Gy or injected with 0.02-0.5 mg/kg apomorphine. The apomorphine effect was also studied in 18 healthy male volunteers. Apomorphine injected to dogs reproduced to a certain extent the pattern and sequence of gastrointestinal, sensorimotor and circulatory lesions constituting the primary radiation reaction. The apomorphilne dosage ED50-ED90, in terms of vomiting, roughly corresponded to irradiation at a dose of 5-10 Gy. The basic difference was that the time of onset and duration of specific symptoms after irradiation were several times longer than after apomorphine injection. It is suggested that the common pathogenetic component in the primary reaction to irradiation and its apomorphine model is the phasic change in the activities of brain dopaminergic systems.

Adult↗
PubMedDate not supplied

Inhibitory effect of apomorphine on hippocampal stimulation-induced "wet-dog shakes" in rats may be due to a stereotyped behavior.

The effect of apomorphine on "wet-dog shakes" (WDS) elicited by hippocampal stimulation was investigated. Apomorphine in doses of 1.0 and 2.0 mg/kg given to rats s.c. reduced the number of WDS. Haloperidol in doses of 0.2-1.0 mg/kg given i.p. also significantly and dose-dependently reduced the number of WDS. The inhibitory effect of apomorphine in doses of 1.0 and 2.0 mg/kg on WDS was completely inhibited by haloperidol given in a dose of 0.5 mg/kg. It is, therefore, conceivable that the inhibition of WDS produced by apomorphine in doses of 1.0 and 2.0 mg/kg may result from the occurrence of stereotyped behavior and that the dopaminergic blocking action may be crucial for the inhibition of WDS induced by hippocampal stimulation. Despite a 50% increase in stimulation intensity, as compared with the afterdischarge threshold, the number of WDS remained unchanged. We tentatively concluded that apomorphine fails to increase the number of WDS, as a result of the ceiling phenomenon.

Animals↗
PubMed1986

Electrophysiological and behavioral assessments of dopamine autoreceptor activation to apomorphine in rats.

Single neuronal activity was recorded extracellularly in the substantia nigra pars compacta (SNC) in rats anesthetized with chloral hydrate. Haloperidol in a dose of 10 micrograms/kg had no significant effects on the SNC neurons. R(-)apomorphine (cumulative i.v. dose of 40 micrograms/kg, given as: 5, 5, 10 and 20 micrograms/kg) inhibited the firing rate of dopaminergic neurons, in a dose-dependent manner. Haloperidol (cumulative i.v. dose of 10 micrograms/kg, as: 2.5, 2.5 and 5 micrograms/kg) reversed the effect of apomorphine. Complete reversal of the firing rate to haloperidol was observed with a dose of 10 micrograms/kg. In rats pretreated with 10 micrograms/kg of haloperidol, there was a dramatic shift to the right of the apomorphine dose-response curve (cumulative i.v. dose of 800 micrograms/kg, as: 50, 50, 100, 200 and 400 micrograms/kg), and this inhibition was reversed by haloperidol (cumulative i.v. dose of 400 micrograms/kg, as: 50, 50, 100 and 200 micrograms/kg). Apomorphine in doses of 40 micrograms/kg and 800 micrograms/kg elicited yawning behavior and stereotypy, respectively. Apomorphine in a dose of 800 micrograms/kg elicited stereotypy in rats treated 3 min before with 10 micrograms/kg of haloperidol. Therefore, electrophysiological determinations of events in the SNC dopaminergic neurons are given support by the behavior observed in these rats.

Animals↗
PubMed1985

The effect of dopamine, apomorphine and piribedil on the mesenterial blood flow of the cat.

Responses to i.v. administration of dopamine, apomorphine, piribedil and bromocriptine were investigated in the feline mesenteric vascular bed. Dopamine increases the mesenterial flow in doses of 0.3 to 30 micrograms/kg; its effect can be inhibited by 1 to 3 mg/kg of sulpiride. Apomorphine and piribedil also increased the blood flow, but only in 20 to 200 times higher doses; they show a tachyphylaxis phenomenon and their maximal activity is 32 and 59 per cent, respectively, that of dopamine. Apomorphine is a partial agonist of dopamine and can inhibit the activity of the transmitter amine. Bromocriptine has no activity on the feline mesenterial flow. The postsynaptic dopamine receptors of the cat can be characterized by the following: strong efficacy of dopamine and lower ones of apomorphine, piribedil and of sulpiride. The presynaptic dopamine receptors are involved mostly in the hypotension, they are activated by low doses of apomorphine, and piribedil and by higher doses of dopamine; sulpiride reacts with these receptors in much lower doses than with the postsynaptic ones.

Animals↗
PubMed1979

Influence of x-ray irradiation on the effects of apomorphine and L-dopa with respect to the dopamine level in rat brain and corpus striatum.

The influence of X-ray irradiation on the dopamine level in brain and in corpus striatum of male albino rats is studied. The changes in the influence of the dopaminergic agonists apomorphine and L-DOPA, applied independently and in combination, on the dopamine level in brain and striatum, are established comparatively (in non-irradiated rats and in rats on the 72nd hour after irradiation with 900 R). Apomorphine is found to have no significant influence on the dopamine level in brain and striatum of non-irradiated rats, while L-DOPA and its combination with apomorphine raise this level. On the 72nd hour after irradiation with 900 R there is no essential change in the dopamine level in brain and the striatum; apomorphine raises the dopamine level in brain and striatum; the effect of L-DOPA and its combination with apomorphine is potentiated with respect to the increase of the dopamine level in brain and striatum.

Animals↗
PubMedDate not supplied

Behavioral effects and cerebral pharmacokinetics of apomorphine in the rat: dependence upon the route of administration.

Effect of the route of administration and satiation on behavioral effects of apomorphine and its pharmacokinetics in the brain was studied in the rat. The highest brain concentration and the strongest behavioral response (gnawing) were observed after a subcutaneous injection of the drug to fasted rats. Intraperitoneal injections produced a more rapid onset of apomorphine action, but lower cerebral concentration of the drug. Intracerebroventricular injections produced a weak effect. Apomorphine administered systemically was eliminated from the brain according to equations for a two-compartment model; the possibility that the long half-time compartment represents the receptor bound apomorphine is discussed. After intracerebroventricular injections apomorphine was eliminated according to equations for the one-compartment open model: the elimination of the drug from the cerebrospinal fluid to circulation was rapid (half-time approx. 9 min).

Animals↗
PubMed1984

Modification of apomorphine-, physostigmine- and pilocarpine-induced yawning after long-term treatment with neuroleptic or cholinergic agents.

Chronic treatment with haloperidol, physostigmine and scopolamine exerted different effects on the frequency of yawning induced by apomorphine (0.25 mg/kg, i.p.), physostigmine (0.2 mg/kg, i.p.) and pilocarpine (4 mg/kg, i.p.) as compared with chronic treatment with saline. Haloperidol decreased the apomorphine- and physostigmine-induced yawning but not the pilocarpine-induced yawning. Physostigmine reduced only the pilocarpine-induced yawning without affecting the apomorphine- and physostigmine-induced yawning. However, physostigmine showed the most rapid onset- and peak-time of yawning induced by a high dose of physostigmine (0.75 mg/kg, i.p.) as well as that of pilocarpine (8 mg/kg, i.p.), and potentiated apomorphine (1 mg/kg, i.p.)-induced stereotypy, as compared with that observed in the saline group. Scopolamine potentiated the physostigmine- and pilocarpine-induced yawning but not the apomorphine-induced yawning. A single pretreatment with scopolamine (0.5 mg/kg, i.p.), however, depressed these yawning responses. The results suggest that yawning induced by physostigmine, but not by pilocarpine, may be modified by long-term treatment with haloperidol. The stereotypy mediated by the postsynaptic dopaminergic system, but not the yawning mediated by the presynaptic system, may be altered by chronic treatment with physostigmine, while long-term treatment with scopolamine seems to produce a supersensitivity to cholinergic receptors.

Animals↗
PubMed1980

[Effect of apomorphine on rat brain opiate receptors].

Stereospecific binding of apomorphine to rat brain opiate receptors was shown by assaying the competition of 7,8(n)--3H--naloxone and D-ala2-tyrosyl-3,5-3H--enkephalin (5-D-leucine) for opiate receptor binding. EC-NaCl50, the concentration of apomorphine which inhibited 50% binding of the radioactive naloxone and D-ala2, D-leu5-enkephalin in the absence of NaCl were 20 and 42 microM, respectively. EC+NaCl 50, the concentration of apomorphine which inhibited 50% binding of the radioactive naloxone in the presence of 100 mM NaCl was 17 microM. From the ratio of EC+NaCl 50 to EC-NaCl the value of "sodium shift" of effective concentration can be calculated as 0.85. From the data obtained it is concluded that apomorphine, like naloxone, is a "pure" antagonist but it has much less affinity for enkephalin and opiate binding sites. The probable mechanisms of the pharmacological action of apomorphine are discussed.

Animals↗
PubMed1984

[Experimental study of the hypotensive effect of apomorphine].

The effects of central (intracisternal: i.c.) and peripheral (intravenous: i.v.) administration of apomorphine (200 micrograms/kg) were compared in chloralose anaesthetized dogs. I.v. or i.c. apomorphine induced a decrease in blood pressure (BP) and an increase in heart rate (HR). However, the decrease in BP was more marked after i.c. route. This effect was due to an activation of presynaptic dopaminergic receptors since it is suppressed by i.v. haloperidol of i.v. phentolamine. I.v. atropine abolished the induced-tachycardia. I.v. but not i.c. domperidone suppressed the hypotensive response to i.v. or i.c. apomorphine. The decrease in BP induced by apomorphine was not found in dogs deprived of adrenal medulla. These results confirm the hypotensive properties of apomorphine and suggest the involvement of peripheral dopaminergic mechanisms in this effect. Dopaminergic agonists may represent a new class of antihypertensive drugs.

Animals↗