Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the rat, oxotremorine increases the threshold for vocalisation after-discharge (affective component of pain reactions) dose dependently at subtremor doses (30-67 mug/kg s.c.). Doses of 225-506 mug/kg were needed to elevate the thresholds for vocalisation and motor response. 1-Tryptophan, PCPA, alpha-methyl-p-tyrosine, 1-Dopa, pimozide and LSD-25 did not affect the antinociceptive activity of oxotremorine, while phenocybenzamine slightly increased the threshold for vocalisation. Oxotremorine did not change the endogenous brain concentrations of noradrenaline and dopamine or 5-HT but decreased that of 5-HIAA in all brain regions at the time of maximal analgesia. The decrease of 5-HIAA was still present after pretreatment with probenecid. After inhibition of tyrosine hydroxylase, oxotremorine accelerated the depletion of dopamine in telencephalic cortex during maximal antinociceptive activity and of noradrenaline in all brain regions at a time when this activity had vanished. Atropine significantly antagonized the analgesic activity of oxotremorine. It is concluded that oxotremorine antinociceptive activity in the rat is related to a cholinergic compoent, while a monoaminergic component is not directly involved.
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PMID:Antinociceptive action of oxotremorine and regional turnover of rat brain noradrenaline, dopamine and 5-HT. 23 55

Adult male Sprague-Dawley rats were given hourly injections of physostigmine for 1--4 h, and the effect of this treatment on dopamine (DA) and noradrenaline (NA) content or on DA and NA was estimated by measuring the decline in these amines produced following the inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (alpha MPT). In later experiments oxotremorine was administered instead of physostigmine at hourly intervals for 2 h. Physostigmine administration resulted in a highly significant increase in the depletion of NA produced by alpha MPT indicating that the turnover of NA was increased by this drug. This effect was observed in the medial basal hypothalamus and anterior hypothalamus but not in the telencephalon-thalamus. Oxotremorine also produced an increase in NA turnover, but this drug was effective in all three brain areas. Atropine pretreatment blocked the effect of both physostigmine and oxotremorine on NA turnover. However, in the case of physostigmine, atropine was only effective if it was given 30 min before each injection of physostigmine. Mecamylamine, a nicotine blocker, did not reverse the effect of physostigmine on NA turnover. These results suggest that there is a cholinergic input via muscarinic receptors which influences the activity of noradrenergic pathways terminating in the anterior or medial basal hypothalamus.
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PMID:Evidence for a cholinergic influence on catecholaminergic pathways terminating in the anterior and medial basal hypothalamus. 48 84

The activity of the enzyme tyrosine hydroxylase (TH) can be increased in the rat superior cervical ganglion by stimulating the preganglionic cervical sympathetic trunk. Since nicotinic, muscarinic and alpha adrenergic receptors have been implicated in ganglionic transmission, the role of each of these receptors in the trans-synaptic regulation of TH activity has been studied. Chlorisondamine, administered at a dose which completely blocks ganglion transmission, blocked the increase in TH activity. Atropine and dihydroergotamine, injected at doses which block peripheral muscarinic and alpha adrenergic receptors, respectively, did not significantly affect the increase in enzyme activity. Thus, of these three receptor systems, only nicotinic receptors seem to play a major role in the increase in TH activity produced by preganglionic nerve stimulation. Simultaneous measurements of tyrosine hydroxylase, dopa decarboxylase and dopamine-beta-hydroxylase activities indicate that both TH and dopamine-beta-hydroxylase activities increase after stimulation of the cervical sympathetic trunk, although dopa decarboxylase activity is unchanged. The time courses of the increase in TH and dopamine-beta-hydroxylase activities were similar, both reaching maximum values 3 days after the end of a 90-min period of nerve stimulation.
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PMID:Increased ganglionic tyrosine hydroxylase and dopamine-beta-hydroxylase activities following preganglionic nerve stimulation: role of nicotine receptors. 610 47

The human gene that codes for the protein alpha-synuclein has been transferred into the Drosophila melanogaster genome. The transgenic flies recapitulate some of the essential features of Parkinson's disease. These include the degeneration of certain dopaminergic neurons in the brain accompanied by the appearance of age-dependent abnormalities in locomotor activity. In the present study, we tested the locomotor response of these transgenic flies to prototypes of the major classes of drugs currently used to treat this disorder. A time course study was first conducted to determine when impaired locomotor activity appeared relative to normal "wild-type" flies. A climbing or negative geotaxis assay measuring the ability of the organisms to climb up the walls of a plastic vial was used. Based on the results obtained, normal and transgenic flies were treated with each of the drugs in their food for 13 days and then assayed. The activity of transgenic flies treated with L-DOPA was restored to normal. Similarly, the dopamine agonists pergolide, bromocriptine, and 2,3,4,5-tetrahydro-7,8-dihydroxy- 1-phenyl-1H-3-benzazepine (SK&F 38393) were substantially effective. Atropine, the prototypical muscarinic cholinergic receptor antagonist, was also effective but to a lesser extent than the other antiparkinson compounds. p-Chlorophenylalanine, an inhibitor of serotonin synthesis, was without beneficial effect as was alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis. This behavioral study further demonstrates the utility of this model in studying Parkinson's disease and reinforces the concept that inhibition of the action of alpha-synuclein may be useful in its treatment as may dopamine D(1) receptor agonists.
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PMID:Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster. 1175 2

The chemical neuroanatomy of the stomatogastric nervous system of the earthworm, Eisenia fetida, has been investigated, using antibodies raised against serotonin, tyrosine hydroxylase, octopamine, GABA, FMRFamide, proctolin, Eisenia tetradecapeptide and neuropeptide Y. Neurons immunoreactive to these antibodies can be observed in the stomatogastric ganglia. The labelled cells comprise altogether 95.4% of the total number of neurons in the ganglion. Immunoreactive projections were followed between stomatogastric individual ganglia as well as towards the enteric plexus. Intrinsic neurons containing the different signal molecules examined are present along the entire length of the enteric plexus, but serotonin immunoreactive perikarya were only found in the hindgut. The density of the different immunoreactive neurons, except the serotonin ones, is highest in the pharyngeal plexus, and the number of labelled neurons decreases along the alimentary canal towards the hindgut. A number of epithelial cells also reveal tyrosine hydroxylase, octopamine, GABA and Eisenia tetradecapeptide immunoreactivity. The action of some putative neurotransmitters, such as dopamine, octopamine, serotonin and proctolin was tested on foregut preparations. Dopamine and octopamine (10(-6)-10(-4) M) have an excitatory effect on the musculature, whereas the effect of serotonin depends on the actual muscle tension. Following precontraction evoked by acetylcholine, serotonin in low concentrations (10(-7)-10(-6) M) causes relaxation, whereas in higher (10(-4) M) concentration it evokes slight contractions. In preparations at basal tone, serotonin (10(-7)-10(-6) M) evokes contractions of the foregut. Atropine strongly inhibits the action of acetylcholine but is ineffective against serotonin, dopamine and octopamine. Similarly, the Na+ channel blocker tetrodotoxin fails to influence the contractile effect of dopamine, octopamine and serotonin. These results suggest that dopamine, octopamine and serotonin act directly on the muscle cells of the alimentary tract. Proctolin do not evoke any significant effect on the foregut.
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PMID:Distribution and action of some putative neurotransmitters in the stomatogastric nervous system of the earthworm, Eisenia fetida (Oligochaeta, Annelida). 1187 79