Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pergolide mesylate is a potent dopamine agonist that is being evaluated clinically in Parkinson disease, hyperprolactinemia, and other diseases. Pergolide activates both presynaptic and postsynaptic dopamine receptors, with some apparent selectivity for the presynaptic dopamine autoreceptors. In rats, low doses of pergolide (0.01 mg/kg or less, intraperitoneally) decreased dopamine turnover in brain, decreased serum prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally), pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of dopamine receptors at various sites, but the data suggest that pergolide may have preferential affinity for presynaptic dopamine receptors. If low doses of pergolide can reduce dopaminergic transmission by activating presynaptic receptors that control dopamine release, then this action might be therapeutically useful in treating schizophrenia without causing tardive dyskinesia or in the treatment of tardive dyskinesia. The long duration of action of pergolide seen in animal and human studies could be an important advantage over some other dopamine agonists such as apomorphine.
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PMID:Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention or treatment of tardive dyskinesia. 717 59

As assessed by changes of prolactin secretion in rat anterior pituitary cells in culture, estrogens can exert a potent antidopaminergic activity at the pituitary level. Androgens and progestins can reverse the effect of estrogens. An interaction of sex steroids at the hypothalamic level on dopamine release and at the pituitary level on dopamine action could also be demonstrated in vivo. Moreover, estrogens exert a similar antidopaminergic activity at the striatal level on dopaminergic-agent-induced acetylcholine accumulation. The observation of a modulation by estrogens of the symptoms of Parkinson's disease and tardive dyskinesias suggests the implication of sex steroids in neurology, psychiatry and behavior.
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PMID:Influence of estrogens on tuberoinfundibular and striatal dopaminergic systems in the rat. 723 54

Circadian rhythms of prolactin have been evaluated in thirteen untreated parkinsonian patients before and after 15 days of treatment with L-Dopa + carbidopa. The 24th secretory pattern was not significatively different from that observed in controls. The L-Dopa + carbidopa therapy does not change the basal circadian prolactin (PRL) rhythm. These results suggest that the tubero-infundibular dopaminergic system (TIDA) and the PRL secretion are conserved in untreated parkinsonian patients (PP). During chronic L-Dopa + carbidopa therapy, the basal PRL levels, evaluated in 21 PP, showed a correlation with the severity of clinical features. The effects of single doses of apomorphine, bromocriptine, lisuride and haloperidol, were studied on serum levels of PRL in 21 PP divided in two groups of "responders" and "non-responders". Haloperidol induced an enhancement of serum PRL; the dopaminergic drugs, apomorphine, bromocriptine and lisuride inhibited basal PRL secretion. It seems that the TIDA system, in Parkinson disease is not significatively altered, even though presenting a remarkable slower response in "non-responders" to L-Dopa therapy. We also evaluated the effect of L-Dopa, L-Dopa + carbidopa, bromocriptine, lisuride, nomifensine and deprenyl on growth hormone secretion in six PP. The endocrine effects of dopaminergic drugs show a mild rise in comparison with controls suggesting an important alteration in the dopamine (DA) control of growth hormone (GH).
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PMID:Prolactin response as an index of dopaminergic receptor function in Parkinson's disease. Correlation with clinical findings and therapeutic response. 726 25

Madopar, a combination of levodopa with benserazide, induced an inconsistent rise in plasma growth hormone in unmedicated patients with Parkinson's disease and in controls, and a greater growth hormone rise in Parkinsonian subjects on chronic Madopar therapy. In subjects on chronic therapy with levodopa and carbidopa (Sinemet), the growth hormone releasing effect of Madopar was blunted. Madopar increased plasma prolactin (PRL) in controls, unmedicated patients and patients on Madopar therapy while in patients on Sinemet therapy the PRL-releasing effect of Madopar was strikingly reduced. Since these data were interpreted as due to a defective dopamine tone in the hypothalamus of Parkinsonian subjects on Madopar but not Sinemet therapy, a direct dopamine receptor agonist, lisuride was administered. Lisuride, however, elicited a blunted growth hormone response both in patients on Madopar and Sinemet therapy, without revealing a state of supersensitivity of dopamine receptors for growth hormone control in Parkinsonian subjects on Madopar therapy. No difference was present in the PRL-lowering effect of lisuride in the different experimental groups. These findings suggest that: (1) hypothalamic dopamine function is impaired in Parkinsonian subjects on Madopar therapy, preserved in unmedicated patients and enhanced in patients on Sinemet therapy; (2) the endocrine effects observed in Parkinsonian subjects on chronic Madopar therapy may be due to some penetration of benserazide across the blood brain barrier in the region of the hypothalamus; (3) since Madopar and Sinemet are in essence equally effective antiparkinsonian remedies, penetration of benserazide does not occur across the blood brain barrier surrounding the nigrostriatal system.
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PMID:Growth hormone and prolactin stimulation by Madopar in Parkinson's disease. 733 6

Ten patients with idiopathic Parkinson's disease (PD) (3 men and 7 women, group A) who had received no treatment for the disease; 102 patients with PD (36 men and 66 women, group B) who had undergone treatment and 45 healthy volunteers (15 men and 30 women, control group) were subject to thyrotropin-releasing hormone (TRH) tests and levodopa tests. In group A basal plasma prolactin (PRL) levels were significantly higher than in the controls both before and during treatment. Peak plasma PRL levels during TRH tests were significantly higher before treatment, but returned to the control levels during treatment. Nadir plasma PRL levels during levodopa tests were significantly increased before and during treatment. In group B basal plasma thyroid-stimulating hormone (TSH) and PRL levels were significantly higher than in the control group. Peak plasma PRL levels during TRH tests and nadir plasma PRL levels during levodopa tests were also significantly increased. The results strongly suggest a disturbance of pituitary hormone secretion due to hypothalamic dysfunction in PD patients.
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PMID:Hypothalamic dysfunction in Parkinson's disease patients. 763 39

We used the PCR amplification technique in an attempt to characterize further the dopamine D2L receptor expressed in the prolactin-secreting pituitary MMQ cell clone, derived from the prolactin- and ACTH-secreting Buffalo rat 7315 alpha pituitary tumour. By semiquantitative PCR amplification we were unable to detect the mRNA encoding the D2S receptor isoform, which derives from the well-known process of alternative splicing, producing two D2 receptor subtypes (D2L and D2S) in such tissues as the anterior pituitary and the corpus striatum. Although the pharmacology of the D2 receptor has been established in many studies on both native receptors and transfected receptor isoforms, because of the lack of tissues naturally expressing only one receptor isoform, MMQ cells represent the first example of cells uniquely or prevalently expressing only the D2L receptor, conceivably coupled to its native transduction mechanisms. These considerations prompted us to evaluate the pharmacology and the second messenger systems known to be modulated by dopamine. Scatchard analysis of [3H]spiperone binding resulted in a linear plot, consistent with the existence of a single class of binding sites, with a Kd of 0.055 +/- 0.002 nM and a Bmax of 27 +/- 3.5 fmol/mg protein. Competition experiments confirmed the GTP-dependence and the order of potency for agonist and antagonist ligands consistent with binding to a D2 receptor. The inhibitory effects of dopamine on adenylyl cyclase activity, inositol phosphate production and intracellular free calcium concentrations, the latter presumably via the opening of K+ channels, and prolactin secretion, as well as the reversal of the effect by the D2-selective antagonist (-)sulpiride and pretreatment with pertussis toxin, are consistent with the known biological actions of dopamine at D2 receptors. Based on our observations, the MMQ cell line can be considered a useful tool for investigating ligand-receptor interactions to develop new selective dopaminergic D2L ligands for the therapy of dopamine-related disorders such as schizophrenia, depression, Parkinson's disease and drug addiction.
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PMID:Absence of D2S dopamine receptor in the prolactin-secreting MMQ pituitary clone: characterization of a wild D2L receptor coupled to native transduction mechanisms. 766 27

Dopamine agonists have been indicated as treatment for disorders such as Parkinson's disease, cardiogenic shock and dopamine insufficiency. A unique relationship exists between dopamine and carcinogenicity. Chronic prolactin stimulation has been identified as a promoter of carcinogenicity. Prolactin secretion is regulated through dopamine receptor activation. Dopaminergic agonists inhibit prolactin release and antagonists increase release. High levels of prolactin have been shown to suppress production of estrogen and progesterone. As a result of these findings, a series of experiments were designed to examine the effects of a specific dopamine agonist, SKF 38393, against MCF-7 cells. MDA-MB231 and MCF-10 cells were used as negative controls. The breast cancer in vitro screening procedure involved the plating of MCF-7, MDA-MB231 and MCF-10 cells in a 96-well plate assay. After 1 day, the cells were exposed to SKF 38393 for 2 days and cell growth was determined by the Alamar blue dye reagent method. The optical density data was analyzed and IC50 values determined. The results indicated that SKF 38393 caused a significant decrease in proliferation of MCF-7 cells. The IC50 value was 0.1 +/- 0.03 microM. The results also indicated no significant effect on MDA-MB231 and MCF-10 cells.
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PMID:The growth inhibitory properties of a dopamine agonist (SKF 38393) on MCF-7 cells. 767 Jan 47

Certain aminotetralins are known to be potent dopamine D2 receptor agonists. N-0923, [-]2-(N-propyl-N-2-thienylethylamino)-5- hydroxytetralin HCl, recognizes the high and low affinity states of the D2 receptor in membranes from bovine caudate with a Klow of 79 nM. The selectivity ratio is D2/D1 = 15 and D2/alpha 2 = 1.4. N-0923 also inhibits dopamine uptake and prolactin secretion, and it is an antagonist at the alpha 2 receptor. N-0923 (3-300 nmol/kg, s.c.) induced dose-dependent contralateral turning behavior in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. The ED50 of 30 nmol/kg was effective for 1 h. The positive enantiomer (N-0924; 300 nmol/kg, s.c.) was without effect. A hemiparkinsonian syndrome was induced in four Macaca nemestrina monkeys by unilateral infusion of the neurotoxin MPTP into the right carotid artery. Video recordings of free-moving behavior revealed bradykinesia, disuse of the contralateral upper limb and turning in a direction ipsilateral to the lesion. N-0923 (3-300 nmol/kg, i.m.) induced contralateral turning behavior, exploratory activity, and contralateral limb usage. The ED50 for turning (30 nmol/kg) was effective for 0.5 h. The potency order for induction of contralateral rotations was (+)-PHNO > N-0923 > bromocriptine. N-0924 (300 nmol/kg, i.m.) was ineffective. We conclude that N-0923 may be useful as a therapeutic agent in the treatment of Parkinson's disease.
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PMID:N-0923, a selective dopamine D2 receptor agonist, is efficacious in rat and monkey models of Parkinson's disease. 791 Sep 48

We report a 68 year old man with a 7 year history of Parkinson's disease (PD) who obtained little benefit from treatment by dopaminergic and anticholinergic agents. During the six months prior to presentation, he experienced more rapid deterioration in symptoms including memory functions, increasing depression, and dystonia of the foot. External application of picoTesla range magnetic fields (MF) resulted in rapid attenuation of tremor and foot dystonia with improvements in gait, postural reflexes, mood, anxiety, cognitive, and autonomic functions. Plasma prolactin and luteinizing hormone (LH) levels rose three days after initiation of treatment. In addition, distinct electroencephalographic (EEG) changes were recorded nine days after two treatments with MF and included enhancement of alpha and beta activities as well as resolution of the theta activity. These findings demonstrate, for the first time, objective EEG changes in response to picoTesla range MF in PD. Since the pineal gland is a magnetosensor and as some of the clinical effects produced by MF such as relaxation, sleepiness, mood elevation, increased dreaming, and enhancement of alpha and beta activities in the EEG have also been noted in healthy subjects administered melatonin, we propose that the clinical effects as well as the EEG changes noted after treatment with MF were mediated by the pineal gland which previously has been implicated in the pathophysiology of PD.
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PMID:The effects of external picoTesla range magnetic fields on the EEG in Parkinson's disease. 808 28

The basal levels of prolactin (PRL) and their changes after i.v. thyrotropin releasing hormone (TRH) administration after bromocriptine (BCT) pretreatment (BCT/TRH test) were monitored in 12 patients with young-onset Parkinson's disease (PD) (before 40 years of age) and 10 patients with older-onset PD (after 40 years of age), as well as in two groups of healthy subjects (10 persons in each), age-matched with older-onset (control A) and young-onset (control B) parkinsonians. The basal PRL levels were normal in both groups of patients. When given after BCT, TRH induced a significantly lower PRL increase in older-onset parkinsonians than in controls. This response was even more blunted in young-onset patients, being significantly more attenuated than in older-onset PD patients.
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PMID:Function of dopamine receptors in young-onset Parkinson's disease: prolactin response. 847 97


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