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levodopa bradycardia

Gillian Douglas, Ashley B Hale, Mark J Crabtree, Brent J Ryan, Alex Hansler, Katrin Watschinger, Steven S Gross, Craig A Lygate, Nicholas J Alp, Keith M Channon
INTRODUCTION: GTP cyclohydrolase I (GTPCH) catalyses the first and rate-limiting reaction in the synthesis of the enzymatic cofactor, tetrahydrobiopterin (BH4). Loss of function mutations in the GCH1 gene lead to congenital neurological diseases such as DOPA-responsive dystonia and hyperphenylalaninemia. However, little is known about how GTPCH and BH4 affects embryonic development in utero, and in particular whether metabolic replacement or supplementation in pregnancy is sufficient to rescue genetic GTPCH deficiency in the developing embryo...
March 1, 2015: Developmental Biology
S V Kuznetsov, L E Dmitrieva, V A Sizonov
Study of parameters of the cardiac, respiratory, and motor activity (MA) was carried out on newborn rat pups for the first day after birth (P0) and at the 14th day of postnatal development (P14) after change of the level of activity of catecholaminergic systems. The animals were administered with L-DOPA (25-100 mg/kg) and the indirect adrenomimetic isoamine (3 and 10 mg/kg). Additionally there were studied effects of L-DOPA and isoamine after blockade of D1 and D2 dopamine receptors (antagonists SCH-23390 and sulpiride)...
July 2012: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
J Antonelle deMarcaida, Steven R Schwid, William B White, Karen Blindauer, Stanley Fahn, Karl Kieburtz, Matthew Stern, Ira Shoulson
Rasagiline is a novel, potent, and selective MAO-B inhibitor shown to be effective for Parkinson's disease. Traditional nonselective MAO inhibitors have been associated with dietary tyramine interactions that can induce hypertensive reactions. To test safety, tyramine challenges (50-75 mg) were performed in 72 rasagiline-treated and 38 placebo-treated Parkinson's disease (PD) patients at the end of two double-blind placebo-controlled trials of rasagiline. An abnormal pressor response was prespecified as three consecutive measurements of systolic blood pressure (BP) increases of >or= 30 mm Hg and/or bradycardia of < 40 beats/min...
October 2006: Movement Disorders: Official Journal of the Movement Disorder Society
N J Crosby, K H O Deane, C E Clarke
BACKGROUND: The tremor of Parkinson's disease can cause considerable disability for the individual concerned. Traditional antiparkinsonian therapies such as levodopa have only a minor effect on tremor. Beta-blockers are used to attenuate other forms of tremor such as Essential Tremor or the tremor associated with anxiety. It is thought that beta-blockers may be of use in controlling the tremor of Parkinson's disease. OBJECTIVES: To compare the efficacy and safety of adjuvant beta-blocker therapy against placebo for the treatment of tremor in patients with Parkinson's disease...
2003: Cochrane Database of Systematic Reviews
K Sato, S Sato, S Ohta, H Mori, S Matsuoka, T Shirai, A Kanazaea, Y Mizuno
We report a 67-year-old man with progressive disturbance of gait. He was well until the spring of 1993 (62 years of the age), when he noted an onset of unsteady gait. He also noted that he started to have a difficulty in playing tennis, in which he became unable to hit the ball with his racket. He also noted parkinsonian features such as bradykinesia and loss of hand dexterity. He was treated with levodopa, which did not improve his symptoms. His MRI revealed marked atrophy of the cerebellum and the pons. The criss-cross high signal lesion was seen in the center of the pons...
July 2000: Nō to Shinkei, Brain and Nerve
T Miyamae, Y Goshima, J L Yue, Y Misu
L-3,4-Dihydroxyphenylalanine (L-DOPA) is probably a transmitter of the primary baroreceptor afferents terminating in the nucleus tractus solitarii; L-DOPA functions tonically to activate depressor sites of the caudal ventrolateral medulla, which receives input from the nucleus tractus solitarii [Misu Y. et al. (1996) Prog. Neurobiol. 49, 415-454]. We have attempted to clarify whether or not L-DOPAergic components within the caudal ventrolateral medulla are involved in baroreflex neurotransmission in anesthetized rats...
1999: Neuroscience
M Nishihama, T Miyamae, Y Goshima, F Okumura, Y Misu
We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Misu Y. et al. (1996) Prog. Neurobiol. 49, 415-454]. Herein, we attempt to clarify whether lesions in the posterior hypothalamic nucleus decrease the tissue content of L-DOPA in the rostral ventrolateral medulla. We also attempt to clarify whether or not endogenous L-DOPA is evoked by electrical stimulation of the posterior hypothalamic nucleus. It is possible that evoked L-DOPA functions as a transmitter candidate to activate pressor sites of the rostral ventrolateral medulla in anesthetized rats...
1999: Neuroscience
K Honjo, Y Goshima, T Miyamae, Y Misu
We have proposed that DOPA is a transmitter of the primary baroreceptor afferents terminating in the rat nucleus tractus solitarii (NTS). GABA is a putative inhibitory neuromodulator for baroreflex inputs in the NTS. GABA may inhibit DOPAergic transmission. Drugs were microinjected into depressor sites of the NTS in anesthetized rats. DOPA (10-60 ng) elicited dose-dependent depressor responses. GABA (3-300 ng) elicited dose-dependent pressor responses. Nipecotic acid (100 ng) elicited pressor responses. Bicuculline (10 ng) elicited depressor responses...
February 12, 1999: Neuroscience Letters
T Sakai, Y Ii, S Kuzuhara
We report sinus bradycardia induced by talipexole hydrochloride in a 65-year-old man with Parkinson disease. Approximately four hours after he had taken 0.8 mg of talipexole hydrochloride, he acutely developed sleepiness, delusion, akinesia, and faintness associated with hypotension and sinus bradycardia. Another similar episode occurred when he had taken talipexole hydrochloride 1.2 mg/day in combination with a daily dose of 200 mg of levodopa and 20 mg of carbidopa. These symptoms persisted for 12 hours and diminished gradually without any specific treatments...
August 1998: Rinshō Shinkeigaku, Clinical Neurology
Y Misu, J L Yue, Y Okumura, T Miyamae, H Ueda
1. L-DOPA as a probable neurotransmitter of baroreceptor afferents functions as a tonic to mediate cardiodepressor control in the nucleus tractus solitarii (NTS). We attempted to clarify further whether a transmitter-like L-DOPA system is altered in NTS of adult spontaneously hypertensive rats (SHR). 2. By microdialysis of left NTS area, the basal L-DOPA release was lower in SHR than in Wistar-Kyoto (WKY) rats. This release was partially inhibited by tetrodotoxin (TTX, 1 mu mol/L) to a similar degree in both strains...
December 1995: Clinical and Experimental Pharmacology & Physiology. Supplement
T Miyamae, J L Yue, Y Goshima, Y Misu
Microinjections of L-threo-dihydroxyphenylserine (L-threo-DOPS, 0.1-3 ng), a synthetic precursor amino acid of noradrenaline, into the medial area of the nucleus tractus solitarii produced dose-dependent depressor and bradycardic responses in anesthetized rats treated with or without i.p. 3-hydroxybenzylhydrazine, a central inhibitor of L-aromatic amino acid decarboxylase. D-threo-DOPS (3 ng) produced no effect. L-Dihydroxyphenylalanine (L-DOPA) methyl ester (1 microgram), a competitive antagonist of L-DOPA, microinjected into the nucleus tractus solitarii, blocked the depressor and bradycardic responses to L-threo-DOPS itself produces vasodepressor actions without its conversion to noradrenaline, probably via a recognition site for L-DOPA in the rat nucleus tractus solitarii...
April 4, 1996: European Journal of Pharmacology
J L Yue, Y Goshima, Y Misu
By microdialysis in the unilateral caudal ventrolateral medulla (CVLM) of anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (L-DOPA) release was in part tetrodotoxin-sensitive or Ca(2+)-dependent and was abolished by i.p. alpha-methyl-p-tyrosine (alpha-MPT), a tyrosine hydroxylase inhibitor. High K+ (50 mM) Ca(2+)-dependently evoked L-DOPA. By unilateral microinjections into the CVLM, L-DOPA (10-100 ng) produced dose-dependent, marked hypotension and bradycardia similarly in rats untreated, treated with i...
September 3, 1993: Neuroscience Letters
J L Yue, Y Goshima, T Miyamae, Y Misu
By microdialysis in the rostral ventrolateral medulla (RVLM) of anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (DOPA) release was partially Ca(2+)-dependent and tetrodotoxin-sensitive and was markedly reduced by alpha-methyl-p-tyrosine (alpha-MPT; 200 mg/kg, i.p.). K+ (50 mM) Ca(2+)-dependently evoked L-DOPA. By microinjections into unilateral RVLM, L-DOPA (30-300 ng) produced dose-dependent hypertension and tachycardia similarly in rats untreated, treated with i.p. 3-hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i...
December 3, 1993: Brain Research
H Harada, M Igarashi, S Sugae, K Okamoto, M Tsuji, T Nakajima
A patient with chronic schizophrenia, who had been treated for a long time with chlorpromazine, haloperidol, levodopa, benserazide hydrochloride, diazepam and biperiden, developed extreme hypothermia (about 32 degrees C) when the dose of haloperidol was increased because of a deterioration of the patient's mental symptoms. No other physical manifestations were observed, except bradycardia. The turnover of noradrenaline in the cerebrospinal fluid and blood was increased in association with the hypothermia in this patient...
September 1994: Japanese Journal of Psychiatry and Neurology
J L Yue, H Okamura, Y Goshima, S Nakamura, M Geffard, Y Misu
We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter and/or neuromodulator in the central nervous system [Misu Y. and Goshima Y. (1993) Trends pharmac. Sci. 14, 119-123]. This study aimed to explore whether or not endogenous L-DOPA, as a neurotransmitter candidate of the primary baroreceptor afferents, tonically functions to activate depressor neurons in the nucleus tractus solitarii of anesthetized rats. By parallel microdialysis in bilateral nucleus tractus solitarii areas, the basal L-DOPA release was in part inhibited by tetrodotoxin perfusion (1 microM) or Ca2+ deprivation, and was markedly reduced by alpha-methyl-p-tyrosine (200 mg/kg, i...
September 1994: Neuroscience
J L Yue, Y Okumura, T Miyamae, H Ueda, Y Misu
We have proposed that L-3,4-dihydroxyphenylalanine (L-DOPA) is a neurotransmitter in the central nervous system [Y. Misu et al. (1995) Adv. Pharmac. 32, 427-459]. L-DOPA as a probable neurotransmitter for the primary baroreceptor afferents tonically functions to mediate cardiodepressor control in the nucleus tractus solitarii and also tonically functions to mediate cardiopressor control in the rostral ventrolateral medulla of rats. We further attempted to clarify whether a transmitter-like L-DOPA system is altered in these areas of adult spontaneously hypertensive rats...
July 1995: Neuroscience
A A Zaĭtsev
Experiments on conscious cats have demonstrated that L-DOPA (25-50 mg/kg) does not change behavioral reactions evoked by dental pulp stimulation. L-DOPA (50 mg/kg) causes bradycardia accompanied by the increase in the cardiochronotropic baroreceptor reflex, inhibits the pressor and enhances heart rate nociceptive reactions. The effect of L-DOPA on the heart rate and baroreceptor reflexes is reversed by preliminary inhibition of peripheral DOPA-decarboxylase with benserazide (30 mg/kg).
November 1982: Farmakologiia i Toksikologiia
A S Tadepalli, C M Prasad
Cats were anaesthetized with a mixture of alpha-chloralose and urethane and artificially ventilated. The spinal cord was transected at the C-1 level and the fourth cerebral ventricle cannulated. Phentolamine (500 microgram) administered into the fourth cerebral ventricle depressed the reflex vagal bradycardic responses elicited by intravenous pressor doses of noradrenaline. Enhancement of reflex bradycardia occurred following intracerebroventricular administration of L-DOPA (3.0 mg) which was reversed by subsequent administration of phentolamine into the fourth cerebral ventricle of spinal cats...
May 1982: Archives Internationales de Pharmacodynamie et de Thérapie
P Johansson, L E Hermansson, M Henning
We have investigated the mediation of the hypotensive action of L-DOPA after peripheral DOPA decarboxylase (DC) inhibition in the sea-gull, Larus argentatus. Vagotomy prevented the bradycardia and hypotension occurring after L-DOPA in birds pretreated with an inhibitor of peripheral DC. L-DOPA alone, given to intact birds, resulted in a slight increase in blood pressure (BP), accompanied by a tendency to bradycardia. Spinal transection in combination with vagotomy reversed the bradycardia and reinforced the increase in BP seen in intact birds after L-DOPA...
June 3, 1983: European Journal of Pharmacology
E Izdebska, A Trzebski
The effects of clonidine (1.5 mcg/kg of body weight), L-DOPA (4 mg/kg) and propranolol (0.1 mg/kg) on the reflex bradycardia caused by stimulation of the arterial baroreceptors were studied in 46 waking cats in encephale isole preparations. The drugs were administered into the vertebral artery. They increased the gain of the cardiovagal reflex from the arterial baroreceptors by 162%, 162.5%, 150% respectively with regard to the control values. A similar effect of clonidine and propranolol was manifested also in cats with spinal cord destroyed between the segments C1 to Th12...
September 1980: Acta Physiologica Polonica
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