Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lithium is currently a major drug used as a treatment for affective disorders and cluster headache, among other conditions. Its mechanism of action remains unknown. The trigeminovascular system may be involved in the pathophysiology of cluster headache and related diseases by liberating neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) in the eye-forehead region. The objective of this study was to investigate whether or not a low concentration of lithium may interfere with peptidergic neuro-transmission at this level. Vasoactive intestinal peptide (VIP), SP, CGRP, capsaicin, and SP+CGRP concentration-response relaxation curves were obtained in the presence and absence of 2 x 10(-4) M lithium in isolated porcine ophthalmic arteries. Lithium inhibited the SP and VIP, but not the CGRP responses. Capsaicin-(a neurotoxin causing release of stored sensory neuropeptides) induced relaxations were partially inhibited by lithium. It is concluded that lithium may interfere with SP- and VIP-induced relaxation. If SP and VIP are of pathogenic significance in cluster headache, lithium may possibly work by counteracting unwanted effects of such peptides.
Headache 1992 Jul
PMID:Lithium inhibits substance P and vasoactive intestinal peptide-induced relaxations on isolated porcine ophthalmic artery. 138 46

Neurotoxic side-effects of tuberculosis chemotherapy occurred in 14.9% of patients with tuberculosis treated prophylactically with intramuscular pyridoxine infusions. Use of small doses of nootropil (piracetam) allowed to control the side-effects (headache and vertigo, sleep disorders, irritation, memory disorders) and to continue treatment with isoniazide, one of the most potent tuberculostatic agents.
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PMID:[The elimination of chemotherapy side effects in pulmonary tuberculosis patients]. 227 76

Tiazofurin (2-B-D-Ribofuranosylthiazole-4-Carboxamide: NSC 286193) is a nucleoside antimetabolite that acts as a potent inhibitor of IMP dehydrogenase resulting in a guanine nucleotide deprivation. Recent in vivo biochemical observations in rats bearing hepatoma suggested a correlation between depletion of guanine nucleotides and antitumor effect. The present phase I trial utilized a weekly x 3 bolus infusion schedule, repeated every 5 weeks. Biochemical measurements of GTP and dGTP were performed in patients at each dose level. Twelve patients received 16 courses of the drug in doses ranging from 1100 to 2050 mg/m2 weekly x 3. The dose limiting toxicities were pericarditis and clinical symptoms suggestive of a more generalized serositis (chest and abdominal pain). Other toxicities included reversible elevations in CPK (MM band only) and SGOT, nausea, vomiting, and arthralgias. Neurotoxic effects were generally mild, including headaches, anxiety, and malaise. Only 1 of 6 patients evaluated for tiazofurin's biochemical activity showed a sustained depletion of guanine nucleotide pools. No antitumor activity was observed. The maximally tolerated dose of tiazofurin on this intermittent weekly x 3 schedule was 1650 mg/m2. Toxicity and the overall lack of biochemical and biologic effect at clinically achievable doses may preclude further clinical evaluation of this drug on a weekly schedule. The toxicities observed in our study were similar to those reported for phase I investigations using a considerably higher dose intensity with daily x 5 schedules.
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PMID:Phase I trial and biochemical evaluation of tiazofurin administered on a weekly schedule. 234 2

Capsaicin application to human nasal mucosa was found to induce painful sensation, sneezing, and nasal secretion. All of these factors exhibit desensitization upon repeated applications. The acute effects induced by capsaicin (300 micrograms/100 microliters) application to the nasal mucosa were studied in healthy volunteers and cluster headache patients. These effects were not different in both nostrils of cluster headache patients as well as in the single nostril of healthy controls. Likewise, the time course of desensitization to the painful sensation and nasal secretion induced by capsaicin applied for five consecutive days in control subjects was almost superimposable to those observed in the nasal mucosa of cluster headache patients. The number of spontaneously occurring attacks was significantly reduced in the 60 days after the end of capsaicin treatment. Whether the beneficial effect induced by capsaicin application to the nasal mucosa could be ascribed to a specific action on sensory neurons remains unknown.
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PMID:Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. 252 Mar 86

Hyperreflectory rhinopathy (HR) is a non-specific hyperreactivity of the nasal mucosa. It causes hypersecretion, decreased nasal patency, sneezing and sometimes headache by local reflexes, which are beyond voluntary control. The synonymous name "vasomotor rhinitis" or "vasomotor rhinopathy" is no longer adequate with regard to our present state of knowledge of the autonomous innervation of the human nasal mucosa. Recent pharmacological investigations show the great importance of peptidergic neurons. In our own studies, the presence and the topical effects of the neuropeptide substance-P in human nasal mucosa are examined. A new concept of the autonomous innervation of the human nasal mucosa is presented. Apart from adrenergic and cholinergic neurons, it also includes peptidergic neurons (SP, CGRP, NKA, VIP, PHI, APP, GRP). According to this model, a hypothesis on the pathogenesis of HR is developed. A key position is occupied by the so-called "axon reflex" which is mediated by substance-P immunoreactive nerve fibers. It is released by a chemical, thermal or mechanical irritation. This axon reflex mediates pain, vasodilation and plasma extravasation (neurogenic oedema), hypersecretion such as smooth muscle contraction, and sneezing reflex. Capsaicin (8-methyl-N-vanillyl-6-nonenamid) leads to a selective degeneration of substance-P immunoreactive nerve fibres and desensitisation of its receptors after repeated topical or systemic application, thus blocking the axon reflex. The risk-free application of capsaicin was shown in self-experiments and in volunteers. Our hypothesis was confirmed by the good results of the treatment of a group of volunteer patients who suffered from HR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New aspects in the pathogenesis and therapy of hyperreflexive rhinopathy]. 305 Mar 40

Neurotoxic volatile organic solvents used by house and car painters may lead to professional toxic encephalopathy after several years of exposure. The symptoms are memory impairment, fatigue, personality changes, headache and dizziness. Vestibular dysfunction was found in 55% of 113 painters examined, mainly in the form of reduced caloric vestibular reactions. No correlation between vestibular dysfunction and the duration of exposure, cerebral atrophy or intellectual impairment could be demonstrated. Vestibular examination may be helpful in detecting early changes in exposed persons and in determining more accurate safety limits for harmful chemicals.
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PMID:Vestibular dysfunction in occupational chronic solvent intoxication. 697 23

Capsaicin, when repeatedly applied to the nasal mucosa of cluster headache patients, has been shown to prevent the occurrence of pain attacks. In order to investigate the mechanism of the drug's action, we evaluated the effect of repeated nasal application of capsaicin on the contents of sensory fibres immunoreactive to substance P and CGRP in the rat nasal mucosa. Further, considering the possible involvement of the cerebral circulation, we verified the effect of a single application of capsaicin on the blood flow velocity of the internal carotid and middle cerebral arteries (of both sides) and the basilar artery, in a group of healthy humans. The measurements were taken using Doppler devices. In order to verify the reproducibility of therapeutic effect of capsaicin, we carried out a 2-year follow-up study on patients affected by cluster headache (17 by episodic form, 8 by chronic form) who responded positively to the first treatment with capsaicin. During this period they were treated again with capsaicin in case of re-occurrence of symptoms. Capsaicin depletes the fibers immunoreactive to substance P and CGRP in the rat nasal mucosa. In the healthy controls, a single application induced vasodilation in the internal carotid, whereas middle cerebral arteries and basilar artery were narrowed. The results of the follow-up study, demonstrates that in 65% of the patients, the beneficial effect of capsaicin was again present when the treatment was repeated. In the chronic patients the therapeutic effect was always transitory (lasting, at maximum one month).(ABSTRACT TRUNCATED AT 250 WORDS)
Headache 1994 Mar
PMID:"Capsaicin-sensitive" sensory neurons in cluster headache: pathophysiological aspects and therapeutic indication. 751 83

Capsaicin was applied unilaterally to the nostril mucosa of 18 episodic cluster headache sufferers in remission. Plasma and saliva levels of substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay. Increase of salivary SP-LI and CGRP-LI as well as of plasma CGRP-LI occurred after capsaicin stimulation. Capsaicin-induced neurochemical changes in saliva and in plasma were compared to the changes observed during cluster headache attacks measured in a separate study. The comparative changes in SP, CGRP and VIP characterizing these two conditions suggest that trigeminal capsaicin-sensitive sensory neurones are unlikely to play any fundamental role in the mechanics of cluster headache.
Cephalalgia 1994 Apr
PMID:Nostril capsaicin application as a model of trigeminal primary sensory neuronal activation. 752 Mar 65

1. The effects of an intravenously administered sumatriptan analogue were examined on c-fos-like immunoreactivity (c-fos-LI), a marker of neuronal activation, evoked within trigeminal nucleus caudalis (TNC) and other brain stem regions 2 h after intracisternal injection of the irritant, capsaicin (0.1 ml, 0.1 mM), in pentobarbitone-anaesthetized Hartley guinea-pigs. 2. C-fos-LI was assessed in eighteen serial sections (50 microns) using a polyclonal antiserum. A weighted average, reflecting total expression within lamina I, IIo of TNC was obtained from three representative levels (i.e., at -0.225 mm, -2.475 mm and -6.975 mm.). 3. Capsaicin caused significant labelling within lamina I, IIo, a region containing axonal terminations of small unmyelinated C-fibres, as well as within the nucleus of the solitary tract, area postrema and medial reticular nucleus. A similar distribution of positive cells was reported previously after intracisternal injection of other chemical irritants such as autologous blood or carrageenin. 4. Pretreatment with a conformationally restricted sumatriptan analogue (with some selectivity for 5-HT1B and 5-HTID receptor subtypes) CP-122,288, reduced the weighted average by approximately 50-60% (P < 0.05) in lamina I, IIo at > or = 100 pmol kg-1, i.v., but did not decrease cell number within area postrema, nucleus of the solitary tract or medial reticular nucleus. A similar pattern was reported previously following sumatriptan, dihydroergotamine or CP-93,129 administration after noxious meningeal stimulation. 5. We conclude that modifications at the amino-ethyl side chain of sumatriptan dramatically enhance the suppression of c-fos expression within TNC, a finding consistent with its remarkable potency against neurogenic plasma protein extravasation within dura mater. CP-122,288 and related analogues may serve as an important prototype for drug development in migraine and related headaches.
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PMID:Suppression by the sumatriptan analogue, CP-122,288 of c-fos immunoreactivity in trigeminal nucleus caudalis induced by intracisternal capsaicin. 778 Jun 55

Neurotoxic syndromes due to occupational solvent exposure present a worldwide health problem, the magnitude of which varies from country to country. Apart from the relatively clear-cut exposure-effect relationships in acute solvent intoxications, those caused by long-term, low-level occupational exposure to solvents are more difficult to detect. Controversial opinions and even debate are frequently encountered in literature on this matter. This is partly due to differences in neurobehavioral methods used, partly to difficulties in obtaining accurate information about exposure. These effects can be studied in humans using biochemical, clinical, and epidemiological methods. It is thus quite conceivable that direct comparison of the results obtained by different methods is not always possible. Moreover, exposure to a variable mixture of solvents is frequent in an occupational setting which is problematic from the toxicological point of view. The clinical pictures of "chronic" occupational solvent intoxications are, with few exceptions, quite nonspecific in nature and share several common features regardless of the underlying chemical exposure. The development of manifest disease is insidious and high interindividual variation of symptoms and signs exists. Some solvents cause primarily peripheral neuropathy. Deterioration in many psychological and neurophysiological functions can be seen. The most common subjective symptoms of solvent intoxication are headache, tiredness, memory disturbances, and dizziness. Clinical findings comprise signs of the central nervous system depression (psychoorganic syndrome, tiredness), dizziness, disturbances in coordination, and general neurasthenic signs. From the clinical point of view, it is important to define the criteria for a diagnosis. In different countries the diagnostic criteria for solvent intoxication may vary considerably, which provides additional difficulties in interpreting the results of studies in this field.
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PMID:Neurotoxic syndromes and occupational exposure to solvents. 843 68


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