Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate (DBcAMP) on the amplitude of the postganglionic action potential during and after a 10 Hz repetitive volley, and 50 to 1000 msec after a conditioning stimulus were investigated. The effects of both drugs on some electrophysiological properties of single cells of the isolated superior cervical ganglia of rats were also studied. At low concentrations of theophylline a reversible potentiation of the compound action potential occurred during and after repetitive stimulation at 10 Hz and also after the single conditioning stimulus. This effect was antagonized by atropine. Large concentrations of theophylline exerted a depressive effect only. Low concentrations of DBcAMP caused a reversible initial depression followed by a durable facilitation of transmission during repetitive stimulation. These concentrations potentiated the action potential amplitude after repetitive stimulation, but depressed it after a single conditioning stimulus. Atropine augmented the latter two effects. DBcAMP at large concentrations depressed transmission, but transmission was facilitated after drug washout. Theophylline and guanosine 3':5'-monophosphate, at ineffective concentrations when used singly, potentiated each other and elicited facilitation which was abolished by atropine. Theophylline and DBcAMP at these concentrations depolarized ganglion cells with a time course shorter than that of the aforementioned effects. Both drugs reduced the frequency and amplitude of the spontaneous miniature excitatory postsynaptic potentials. Theophylline did not increase the evoked transmitter release appreciably. On the basis of these findings and the evidence from literature, it is suggested that the reversible facilitatory effect of theophylline may be at least in part due to inhibition of phosphodiesterase of the ganglion cells leading to an enhanced muscarinic transmission. The prolonged facilitatory effect of DBcAMP may result from a durable change in the postsynaptic membrane structure leading to enhanced muscarinic transmission. An enhancement in the muscarinic transmission by both drugs increases the membrane excitability causing recruitment of subthreshold depolarized cells to discharge resulting in facilitation.
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PMID:Effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate on sympathetic ganglionic transmission in rats. 20 71

The in vitro effects of theophylline and aminogluthetimide upon basal and ACTH stimulated cAMP, cortisol and aldosterone responses of normal human adrenocortical tissue were evaluated. Theophylline increased basal cAMP levels and cortisol output, however, basal aldosterone output was depressed. Theophylline in concert with ACTH depressed cortisol and aldosterone output. Aminogluthetimide alone did not affect basal cAMP levels, however, the normal cAMP response to ACTH was delayed in aminogluthetimide pre-treated adrenals. Aminogluthetimide also depressed basal and ACTH stimulated cortisol and aldosterone output with the latter being more sensitive. The findings indicate that both theophylline and aminogluthetimide produce effects upon the adrenal in addition to inhibition of phosphodiesterase and cholesterol side-chain cleavage, respectively. Further, theophylline depression of ACTH stimulated steroid output may be helpful in understanding the interplay between a number of factors in the control of adrenal steroid biosynthesis and release.
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PMID:In vitro effects of theophylline and aminogluthetimide upon basal and ACTH induced cAMP levels and steroid output by the normal human adrenal gland. 20 41

Interactions between some substances (theophylline, noradrenaline, imidazole, ouabain and verapamil) and adenosine or adenosine triphosphate (ATP) were examined by recording the twitch tension of partially magnesium blocked phrenic-rat diaphragm preparations stimulated indirectly. Theophylline (an inhibitor of phosphodieterases) prevented and reversed the neuromuscular depression induced either by adenosine or ATP, and these substances antagonized the neuromuscular facilitation caused by imidazole (an activator of phosphodiesterases); noradrenaline and ouabain did not modify and verapamil increased that depression. These results indicate that the putative purine presynaptic receptor is not the ATPase, that it does not appear to operate by implication of cyclic AMP, but that it could mediate a process involved in the reduction of transmitter release by regulating the entry of calcium that follows the depolorization of the motor nerve endings.
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PMID:Purine effects at the neuromuscular junction and their modification by theophylline, imidazole and verapamil. 47 9

The action of 21 purine compounds on the twitch response of the electrically stimulated guinea pig isolated ileum has been investigated. Adenosine and related compounds produced a dose-dependent depression of the response. Adenosine was the most potent and 2'-deoxyadenosine had one hundredth the potency of adenosine. Adenine, hypoxanthine, inosine, IMP, ITP, xanthine, xanthosine, XMP, XTP, guanine, GMP and GTP were ineffective at concentrations less than 1 mM. Adenosine (30 microgram) reduced the electrically induced ACh output from the ileal strips. The dose--depression curve for adenosine (0.1--30 microgram) was shifted to the right in the presence of xanthine derivatives and of these, theophylline was the most potent inhibitor of adenosine. On the other hand, dipyridamole (0.1--1 microgram) and hexobendine (0.1--1 microgram) shifted the curve to the left. They markedly inhibited 3H-adenosine uptake into the ileum. Theophylline (0.1 mM), dipyridamole (0.3 microgram) and hexobendine (0.3 microgram) did not affect tetrodotoxin-, adrenaline-, strychnine- and morphine-induced inhibition of the twitch response. The present investigations have revealed that adenosine and related compounds reduce ACh release from the intramural cholinergic nerves in the guinea pig ileum possibly in a specific manner (or through a specific receptor site) different from that of other inhibitors such as morphine.
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PMID:Effects of purine compounds on cholinergic nerves. Specificity of adenosine and related compounds on acetylcholine release in electircally stimulated guinea pig ileum. 63 57

Adenosine and adenine nucleotides [adenosine-5'-monophosphate, adenosine-5'-diphosphate, adenosine triphosphate (ATP), cyclic adenosine 3',5'-monophosphate (dbcAMP)], but not (cAMP) and dibutyryl cyclic adenosine 3',5'-monosphosphate (dbcAMP)], but not adenine or inosine, inhibited the twitch response of the electrically stimulated guinea-pig myenteric plexus-longitudinal muscle preparation. With each agent except dbcAMP, inhibition was manifest muscle preparation. With each agent except dbcAMP, inhibition was manifest from 1 to 500 muM was maximal within 1 minute. For dbcAMP, higher concentrations were required (10-fold increase) and inhibition was maximal after 20 to 30 minutes. Theophylline (0.05-0.5 mM) both reversed and prevented the inhibition produced by each of these agents. In higher concentrations (greater than 1 mM), theophylline itself depressed the twitch response. Neither propranolol nor phenoxybenzamine altered theophylline-induced depression, whereas phenoxybenzamine did not alter adenosine-induced inhibition. Adenosine, ATP, cAMP and theophylline (0.25 mM) did not alter acetylcholine-induced contractions, whereas a higher concentration of theophylline (2.5 mM) inhibited contractions. Theophylline (up to 0.5 mM) did not antagonize epinephrine- or dopamine-induced inhibition of the twitch response, but did antagonize morphine-induced inhibition. These findings suggest that adenosine and related nucleotides act at a common receptor site at which theophylline acts as a competitive antagonist and that there is a link between morphine and adenine nucleotide action in this preparation.
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PMID:Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline. 127 Dec 86

Theophylline has been associated with a variety of behavioral side effects in asthmatic children. This study was a 6-month investigation of the relationship between theophylline treatment and psychological changes in 8 to 16 year old asthmatic children. Included were a group receiving theophylline (n = 19), a control group not receiving theophylline (n = 44), and a nonasthmatic control group (n = 24). The three groups had similar age, socioeconomic status, and IQ. The two groups of children with asthma demonstrated greater emotional dysfunction, characterized by tendency toward withdrawal and depression, than the nonasthmatic control group. Each of five assessment appointments (baseline and 1 week, 1 month, 3 months, and 6 months after beginning theophylline treatment) included measures of pulmonary function, attention, impulsivity, memory, fine motor control, activity level, self-reported mood, and parental observation of difficult behavior. Pulmonary functions were lower in the theophylline group at baseline but improved significantly after commencement of theophylline therapy. Over the 6-month interval, children in the theophylline group demonstrated improved scores on a laboratory measure of attention, while their parents reported increased conduct problems and hyperactivity. On the whole, psychological score changes were subtle, and no other between-group differences emerged in the remaining laboratory measures.
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PMID:Psychological change associated with theophylline treatment of asthmatic children: a 6-month study. 175 45

The possible relationship between circulating immune complexes (CIC) and peripheral T lymphocyte populations was studied in thirteen active multibacillary leprosy (10 lepromatous--LL--and 3 borderline lepromatous--BL--) and 19 matched controls. Theophylline-resistant T cells (The-R, a lymphocyte subpopulation displaying helper activity on B cells) and total T cells were assessed by means of the E rosette technique, with and without previous theophylline incubation, 1h 37 degrees C, respectively. CIC were quantified by 125I-C1q binding test. Although leprosy patients showed a statistical non significant light depression in total T cells the remarkable variability in circulating levels of The-R T cells enabled us to separate them into two well delineated groups (in relation to this variable p less than 0.001) with no difference in age, sex and bacteriologic state: a) leprosy patients with The-R T cells proportionally conserved (6LL and 2BL); b) leprosy patients with The-R T cells proportionally depressed (4LL and 1BL). Patients belonging to the latter group showed the highest statistically significant levels of CIC. Even though we do not discard an unknown factor being responsible for our findings, we believe that this inverse relationship between elevated CIC and depressed The-R circulating T cells might be representing a lower helper activity on antibody synthesis intending to reduce its excessive production.
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PMID:T lymphocyte subpopulations in leprosy patients and their relation with circulating immune complexes. 214 69

Theophylline overdosage can cause life-threatening symptoms, that include seizures and cardiac arrhythmias, and can be fatal. Neither the onset of toxicity nor the severity of symptoms is well predicted by serum theophylline concentrations. Since depressed vitamin B6 plasma levels can occur in patients receiving theophylline, we explored a B6-theophylline interaction in a rabbit model. Administration of theophylline preparations intraperitoneally (aminophylline) or orally (sustained release anhydrous theophylline) resulted in a 47% depression of plasma pyridoxal 5'-phosphate (PLP) levels. The 87% increase in PLP with pyridoxine administration was only 18% when aminophylline was also given. The mechanism of the theophylline-B6 interaction is obscure. Ethylenediamine in some theophylline preparations binds directly to PLP, potentially increasing the less direct theophylline effect. Pyridoxine supplementation resulted in higher average PLP levels but did not prevent death in animals with profoundly low PLP levels. If these data apply to humans, B6 deficiency may contribute to chronic theophylline toxicity; however, pyridoxine administration in the dosage used may not prevent toxicity. Larger doses may prove beneficial after further investigation.
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PMID:Depression of vitamin B6 levels due to theophylline. 236 33

Submerged rat hippocampal slices were exposed to hypoxic medium prepared with 95% N2/5% CO2. The population spikes recorded from CA1 cell layer were completely blocked within a range of 5-10 min. The adenosine antagonist theophylline (100 microM) delayed and partially prevented the hypoxia-induced depression. Increasing concentrations of the more potent adenosine antagonist 8-phenyltheophylline (8-PT; 0.1, 1, 10 microM) resulted in progressively less hypoxia-induced depression. The antidromically elicited afterpotentials recorded in the absence of synaptic transmission in low calcium, high magnesium medium were blocked within 8 min of hypoxia. Theophylline (100 microM) and 8-PT (10 microM) delayed to a similar extent the hypoxia-induced depression of the first afterpotential but did not prevent its complete depression.
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PMID:Adenosine antagonists delay hypoxia-induced depression of neuronal activity in hippocampal brain slice. 276 71

The purpose of these studies was to evaluate the short-term toxicity of theophylline, a compound present in tea and used in a variety of clinical applications. Fourteen-day repeated-dose toxicity studies were conducted in B6C3F1 mice and F344 rats of both sexes. Theophylline was administered in feed (0, 500, 1000, 2000, 4000, and 8000 ppm) or by gavage in corn oil (12.5-twice daily, 25, 50, 50-twice daily, 100, 200, 200-twice daily, and 400 mg/kg). Dosed-feed exposure to theophylline at concentrations up to 8000 ppm induced no significant toxicity except for dose-related uterine hypoplasia in rats. Palatability problems at that level precluded administration of higher concentrations. In the gavage study, 400 mg/kg was acutely toxic for both species, but mice and rats differed in that this same daily dose administered as two separate doses of 200 mg/kg was acutely toxic in rats but not in mice. No dose-related weight gain depression was evident in mice; weight gain was depressed in the majority of dose levels in rats and was pronounced at the higher levels. Clinical signs in mice were squinting and distended testes in males, and in rats, rapid respiration (all doses), squinting, and hunching. Gross necropsies, organ weights, clinical pathology, and pathology identified no target organs in mice, while histopathologic observations in rats suggested heart and stomach as possible target organs. Histopathologic effects in a number of other tissues, including lung, thymus, bone marrow, spleen, and uterus, were considered to reflect agonal changes in treated rats, possibly related to inanition. The results suggest that both species and sex differences exist with respect to sensitivity to theophylline toxicity, with F344 rats being more sensitive than B6C3F1 mice and male rats being more sensitive than female rats.
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PMID:Studies on the short-term toxicity of theophylline in rats and mice. 337 86


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