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

L-DOPA is proposed to be a neurotransmitter and/or neuromodulator in CNS. It is released probably from neurons, which may contain L-DOPA as an end-product, and/or from some compartment other than catecholamine-containing vesicles. The L-DOPA itself produces presynaptic and postsynaptic responses. All are stereoselective and most are antagonized by competitive antagonist. In striatum, L-DOPA is neuromodulator, mother of catecholamines, not only a precursor for dopamine but also a potentiator of children for presynaptic beta-adrenoceptors to facilitate dopamine release and postsynaptic D2 receptors, and ACh release inhibitor. All may cooperate for Parkinson's disease. Meanwhile, supersensitization of increase in L-glutamate release to nanomolar levodopa was seen in Parkinson's model rats, which may relate to dyskinesia or "on-off" during chronic therapy. In lower brainstem, L-DOPA tonically activates postsynaptic depressor sites of NTS and CVLM and pressor sites of RVLM. L-DOPA is probably a neurotransmitter of primary baroreceptor afferents terminating in NTS. GABA, the inhibitory neuromodulator for baroreflex in NTS, tonically functions to inhibit, via GABAA receptors, L-DOPA release and depressor responses to levodopa. Levodopa inversely releases GABA. L-DOPAergic monosynaptic relay from NTS to CVLM and from PHN to RVLM is suggested. Tonic L-DOPAergic baroreceptor-aortic nerve-NTS-CVLM relay seems to carry baroreflex information. Disturbance of neuronal activity to release L-DOPA in NTS, loss of the activity in CVLM, enhancement of the activity with decreased decarboxylation and increase in sensitivity to levodopa in RVLM may be involved in maintenance of hypertension in SHR. This is a story of "L-DOPAergic receptors" with extremely high affinity and low density.
 ...
PMID:Neurobiology of L-DOPAergic systems. 889 95

Over an 18-month period, all incident cases of neurological disorders were ascertained prospectively in an unselected urban population based in 13 general practices in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery. In three of these practices, the lifetime prevalence of neurological disorders was also assessed. A population of 100 230 patients registered with participating general practices was followed prospectively for the onset of neurological disorders. Multiple methods of case finding were used to maintain accuracy. The age- and sex-adjusted incidence rates of neurological disorders were calculated. The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients. The age- and sex-adjusted incidence rates were calculated for major neurological conditions. [These are expressed as rates per 100 000 persons per annum, with 95% confidence intervals (CI) in parentheses]. The commonest of these were first cerebrovascular events, 205 (CI: 183, 230); shingles, 140 (CI: 104, 184); diabetic polyneuropathy, 54 (CI: 33, 83); compressive neuropathies, 49 (CI: 39, 61); epilepsy, 46 (CI: 36, 60); Parkinson's disease, 19 (CI: 12, 27); peripheral neuropathies, 15 (CI: 9, 23); CNS infections, 12 (CI: 5, 13); post-herpetic neuralgia, 11 (CI: 6, 17); and major neurological injuries, 10 (CI: 4, 11). Lifetime prevalence rates are also reported (expressed as rate per 1000 persons with 95% CI). The most prevalent conditions were: completed stroke, 9 (CI: 8, 11); transient ischaemic attacks, 5 (CI: 4, 6); active epilepsy, 4 (CI: 4, 5); congenital neurological deficit, 3 (CI: 3, 4); Parkinson's disease, 2 (CI: 1, 3); multiple sclerosis, 2 (CI: 2, 3); diabetic polyneuropathy, 2 (CI: 1, 3); compressive mononeuropathies, 2 (CI: 2, 3); and sub-arachnoid haemorrhage, 1 (CI: 0.8, 2). Overall, the onset of 625 neurological disorders was observed per 100 000 population annually. Six percent of the population had at some time had a neurological disorder. This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times; we found that these disorders give rise to significant morbidity in the community.
 ...
PMID:The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. 1073 97

Every month new clinical trials are published that provide relevant insight into medical care. Health care professionals are expected to review the results of these trials to update their knowledge and clinical practice. Although it is impossible to review every clinical trial, it is important to evaluate study findings in one's area of interest or practice. For nurses and other practitioners in the field of geriatrics, clinical trials involving drug therapy can be particularly valuable. This article is a review of clinical trials published in the past year that provide new information about drug therapy used by elderly patients. It reviews recent clinical trials in the areas of cardiology (hypertension, dyslipidemia, antioxidants for cardiovascular disease, hormone replacement therapy, atrial fibrillation, systolic heart failure), hematology (venous thromboembolic disease), neurology (Parkinson's disease, post-herpetic neuralgia), and rheumatology (osteoarthritis). Major findings and implications for geriatric clinical practice are included.
 ...
PMID:What's new about old drugs. 1475 53

As people grow old, their need for medications increases dramatically because of the higher incidence of chronic pain, diabetes mellitus, cardiovascular and neurological diseases in the elderly population. Furthermore, the elderly require special consideration with respect to drug delivery, drug interactions and adherence. In particular, patients with chronic neurological diseases often require multiple administration of drugs during the day to maintain constant plasma medication levels, which in turn increases the likelihood of poor adherence. Consequently, several attempts have been made to develop pharmacological preparations that can achieve a constant rate of drug delivery. For example, transdermal lisuride and apomorphine have been shown to reduce motor fluctuations and duration of 'off' periods in advanced Parkinson's disease, while rotigotine allows significant down-titration of levodopa without severe adverse effects. Thus, parkinsonian patients with long-term levodopa syndrome or motor disorders during sleep could benefit from use of transdermal lisuride and apomorphine. Moreover, transdermal dopaminergic drugs, particularly rotigotine, seem the ideal treatment for patients experiencing restless legs syndrome or periodic limb movement disorder during sleep, disorders that are quite common in elderly people or in association with neurodegenerative diseases. Unlike dopaminergic drugs, transdermal treatments for the management of cognitive and behavioural dysfunction in patients with Parkinson's disease and Alzheimer's disease have inconsistent effects and no clearly established role. Nevertheless, because of their favourable pharmacological profile and bioavailability, the cholinesterase inhibitors tacrine and rivastigmine are expected to show at least the same benefits as oral formulations of these drugs, but with fewer severe adverse effects. Transdermal delivery systems play an important role in the management of neuropathic pain. The transdermal lidocaine (lignocaine) patch is recommended as first-line therapy for the treatment of postherpetic neuralgia. Furthermore, in patients with severe persistent pain, transdermal delivery systems using the opioids fentanyl and buprenorphine are able to achieve satisfactory analgesia with good tolerability, comparable to the benefits seen with oral formulations. Transdermal administration is the ideal therapeutic approach for chronic neurological disorders in elderly people because it provides sustained therapeutic plasma levels of drugs, is simple to use, and may reduce systemic adverse effects. Several transdermal delivery systems are currently under investigation for the treatment of Parkinson's disease, Alzheimer's disease and neuropathic pain. Although most transdermal delivery systems treatments cannot be considered as first-line therapy at present, some of them provide clear advantages compared with other routes of administration and may become the preferred treatment in selected patients. In general, however, most transdermal treatments still require long-term evaluation in large patient groups in order to optimise dosages and evaluate the actual incidence of local and systemic adverse effects.
 ...
PMID:Transdermal treatment options for neurological disorders: impact on the elderly. 1682 90

Postherpetic neuralgia (PHN) is a chronic pain syndrome and one of the most common complications of herpes zoster. Although the pathophysiological mechanisms involved in PHN are still largely unknown, it seems reasonable to assume that there are lesions of the peripheral afferent pain pathways and inflammation-induced damage to afferent ganglia in the spinal cord. Growing body of evidence indicates that the glial cells, particularly microglia (CNS macrophages) and astrocytes are activated following peripheral and central noxious insult and their activation is thought to play an important role in central sensitization. Glial modulators showed antiallodynic and antihyperalgesic properties in various models of experimental pain. Minocycline is a semisynthetic second generation tetracycline that exerts neuroprotection effect. It has been shown to be effective in preventing sciatic inflammatory neuropathy and intrathecal HIV-1gp120 associated pain behaviors. This agent has been used recently as a selective microglial inhibitor since it prevents microglial activation and disease progression in experimental allergic encephalomyelitis, an animal model of multiple sclerosis and other neurodegenerative diseases, such as amyotropic lateral sclerosis and Parkinson's disease. Therefore, we hypothesize that minocycline might attenuate postherpetic neuralgia by specifically inhibiting the activation and metabolism of glial cells.
 ...
PMID:Minocycline may attenuate postherpetic neuralgia. 1946 72

In 2013, perampanel is approved as an add-on treatment for generalised and focal seizures in pharmaco-resistant epilepsy. New anticoagulants are superior to antivitamin K in stroke secondary prevention in case of atrial fibrillation. DBS remains a valid therapeutic option for advanced Parkinson's disease. Intranasal ketamine seems to reduce the intensity of severe migraine aura. High concentrations of topic capsaicin improve post-herpetic neuralgia. In Alzheimer's disease, statins might deteriorate cognitive functions. Oral immuno-modifing treatments for relapsing remitting multiple sclerosis have shown to slow cerebral atrophy progression at two years.
 ...
PMID:[News in neurology 2013]. 2455 5

Neuropathic pain may be caused by a variety of lesions or diseases of both the peripheral and central nervous system. The most common and best known syndromes of peripheral neuropathic pain are painful diabetic neuropathy, trigeminal and post-herpetic neuralgia, persistent post-operative and post-traumatic pain, complex regional pain syndrome, cancer-related neuropathic pain, HIV-related neuropathic pain and pain after amputation. The less common central pain comprises primarily central post-stroke pain, pain after spinal cord injury, central pain in Parkinson disease or in other neurodegenerative diseases, pain in syringomyelia and in multiple sclerosis. A multidisciplinary team of Polish experts, commissioned by the Polish Association for the Study of Pain and the Polish Neurological Society, has reviewed the literature on various types of neuropathic pain, with special focus on the available international guidelines, and has formulated recommendations on their diagnosis and treatment, in accordance with the principles of evidence-based medicine (EBM). High quality studies on the efficacy of various medicines and medical procedures in many neuropathic pain syndromes are scarce, which makes the recommendations less robust.
...
PMID:Diagnosis and management of neuropathic pain: review of literature and recommendations of the Polish Association for the Study of Pain and the Polish Neurological Society - Part Two. 2548 54

The prevalence of temporomandibular disorder (TMD) among elderly people with Parkinson's disease (PD) is relatively high, but a population-based study of the relationship between PD and TMD is still lacking. This study, therefore, sought to investigate the association between TMD and PD by using data for one million randomly sampled beneficiaries of Taiwan's National Health Insurance program, including 6,185 PD patients who were matched through propensity score matching with 18,555 non-PD patients. Both the PD and non-PD cohorts were followed until death, any diagnosis of TMD, or December 31, 2013, whichever occurred first. Each diagnosis of TMD was made by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnosis codes 524.60, 524.62, 524.63, and 524.69 while excluding tooth abscess, wisdom tooth eruption, herpes zoster and postherpetic neuralgia, mastoiditis, otitis externa, otitis media, parotitis, sialadenitis, and trigeminal neuralgia. We used Cox proportional hazard regression models to calculate the relative risk of TMD and found a 2.11-fold (95% CI: 1.35-3.30) increased risk of TMD overall in the PD group compared with the non-PD group. Stratified by follow-up period, there was a 4.25-fold (95% CI: 1.51-11.93) increased risk in the PD group in the first year after the initial PD diagnosis and a 3.88-fold (95% CI: 1.33-11.28) increased risk in the second year. Over the long-term (>5 years), PD was significantly associated with an increased risk of TMD. These findings suggest that it is important to closely monitor the temporomandibular joint health of PD patients.
 ...
PMID:The association between Parkinson's disease and temporomandibular disorder. 3119 37

The authors report on a female patient with left-dominant Parkinson's disease with motor fluctuations and levodopa-induced dyskinesias and comorbid postherpetic neuralgia (PHN), who underwent a right-sided pallidotomy. Besides a substantial improvement in her Parkinson's symptoms, she reported an immediate and complete disappearance of PHN. This neuralgia had been long-standing, pharmacologically refractory, and severe (preoperative Brief Pain Inventory [BPI] pain severity score of 8.0, BPI pain interference score of 7.3, short-form McGill Pain Questionnaire sensory pain rating index of 7 and affective pain rating index of 10, Present Pain Intensity rank value of 4, and visual analog scale score of 81 mm; all postoperative scores were 0). She continued to be pain free at 16 months postoperatively.This peculiar finding adds substantially to the largely unrecognized evidence for the role of the pallidum in pain processing, based on previous electrophysiological, metabolic, anatomical, pharmacological, and clinical observations. Therefore, the potential of the pallidum as a neurosurgical target for neuropathic pain warrants further investigation.
 ...
PMID:Complete resolution of postherpetic neuralgia following pallidotomy: case report. 3156 Dec 24

Electro-modulation of subcortical deep brain structures by surgically implanted electrodes is now standard evidence-based treatment for movement disorders such as Parkinson's disease and essential tremor and is approved for dystonia and obsessive-compulsive disorder under a humanitarian exemption. Historically, deep brain stimulation (DBS) for multiple indications has demonstrated acceptable complication rates, rare mortality, and reducing morbidity as the technology and the techniques of its application have advanced. DBS for the amelioration of pain has been performed since the early 1950s, and became widely used in the 1970s, when targeting the somatosensory thalamus was shown to be efficacious for intractable pain syndromes including facial pain. The technique fell out of favour in the late 1990s after 2 multicentre trials failed to meet end-point criteria. Since these trials, DBS for pain has remained for investigational or "off-label" use. Criticisms from previous literature have involved unsuitability of patient selection, as well as inconsistencies in neurosurgical technique. Clinical success with DBS for facial pain has been for the treatment of a variety of chronic neuropathic and nociceptive pain syndromes; including trigeminal neuropathy, post-herpetic neuralgia, deafferentation facial pain, "atypical" facial pain, cluster headaches and other trigeminal autonomic cephalalgias, as well as head and neck pathologies, most often which have been resistant to all other 1st- and 2nd-line medical and surgical treatments, when DBS has become a "last treatment option." An enhanced understanding of the mechanisms of action of DBS for pain will enhance outcome, and appropriately prescribe evolving novel nuclear brain targets.
 ...
PMID:Deep Brain Stimulation for Facial Pain. 3290 39


1