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 literature regarding the intrathecal use of morphine, baclofen, and midazolam to treat spasticity is reviewed. Nine patients with significant spasticity due to different etiologies were treated. Morphine and midazolam decreased spasticity but did not change the patient's functional status. Baclofen improved patient status, but was associated with significant CNS depression in two cases.
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PMID:Intrathecal application of drugs for muscle hypertonia. 304 64

The effects of withdrawal from long-term treatment with increasing concentrations of sodium barbital in the drinking water were studied in rats. Animals were tested 72 hr after the removal of the drug. Withdrawal of barbital induced a significant leftward displacement of the dose-response curves obtained for the convulsive effects of strychnine, picrotoxin and 3-mercaptopropionic acid. The removal of the drug also made the rats more sensitive to convulsions elicited by sound. Baclofen and THIP were able to decrease the audiogenic response score of rats, withdrawn from barbital, in a dose-dependent way. These effects were interpreted to be a consequence of changes in the sensitivity of central GABAA and/or noradrenergic receptors induced by depression due to long-term administration of barbital.
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PMID:Central nervous system supersensitivity and withdrawal from long-term treatment with barbital. 409 60

1 The effect of thiopentone, methohexitone, urethane and ketamine on the uptake and release of gamma-aminobutyric acid (GABA) and D-aspartate by rat thalamic slices has been investigated. 2 A high, supra-anaesthetic concentration of methohexitone increased the uptake of both D-aspartate and GABA. 3 None of the anaesthetics used had any detectable effect upon the spontaneous release of either amino acid. 4 Urethane and ketamine had no effect upon the K+-stimulated release of either amino acid. 5 Methohexitone and thiopentone produced a biphasic dose-response on the K+-stimulated release of both amino acids; low concentrations enhanced release, high concentrations depressed release. 6 Bicuculline hydrochloride and picrotoxin both significantly reduced the barbiturate-induced enhancement of K+-stimulated amino acid release, but did not significantly alter the depression of K+-stimulated release at higher barbiturate concentrations. 7 Baclofen, either alone (1 microM to 1 mM), or tested against the barbiturates, had no detectable effect.
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PMID:The effects of anaesthetics on the uptake and release of amino acid neurotransmitters in thalamic slices. 612 80

The effect of baclofen on gamma motoneurones supplying gastrocnemius medialis muscle in the rabbit has been investigated. Baclofen was found to decrease the frequency of firing of tonic gamma motoneurones, and in some cells to inhibit the tonic discharge altogether. Baclofen also increased the regularity of tonic gamma motoneurone discharge. The drug was found to raise the threshold for firing of gamma motoneurones in response to electrical stimulation of the sural nerve, indicating a depression of reflex transmission between the sural nerve and the motoneurones. The results are discussed and brief consideration given to the possible consequences of these results for the action of the drug in human spasticity.
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PMID:The effects of baclofen on gamma motoneurones supplying gastrocnemius muscle in the rabbit. 621 17

The relationship of the depressant effect of baclofen on spinal monosynaptic transmission and its effect on the excitability of primary afferents was examined in spinal unanesthetized cats. Baclofen (1.0 mg/kg, i.v.) produced a deep and long-lasting depression of spinal reflex responses with a concomitant decrease of terminal excitability. Primary afferent depolarization, as indicated by an increase of terminal excitability, evoked by conditioning of an antagonistic muscle nerve, was greatly reduced by this drug. Depression of monosynaptic transmission induced by baclofen was temporarily reversed by posttetanic potentiation. However, the same high frequency orthodromic stimulation further reduced excitability of terminals. It is therefore unlikely that block of terminal invasion is responsible for baclofen-induced depression of spinal monosynaptic transmission. These results are compatible with the suggestion that baclofen causes a reduction of transmitter release. In the spinal cord, this action is probably limited to the excitatory transmitter of primary afferents.
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PMID:Baclofen-induced decrease of excitability of primary afferents and depression of monosynaptic transmission in cat spinal cord. 628 27

1 The effects of gamma-aminobutyric acid (GABA) and related drugs on the isolated anococcygeus muscle of the rat were determined. 2 GABA caused a dose-related inhibition of the electrically-evoked twitch response. 3 The maximum response to GABA was a 56.8% depression of twitch response, with an EC50 of 0.68 microM. 4 (+/-)-Baclofen mimicked the effect of GABA (EC50 0.9 microM). (+)-Baclofen was more than 100 times less active than (--)-baclofen. 5 The response to GABA was unaffected by picrotoxin or bicuculline but was antagonized by 5-aminovaleric acid (0.5) mM). 6 Our results suggest that GABAB receptors are present on motor nerve terminals in the rat anococcygeus muscle and that 5-aminovaleric acid is an antagonist of these receptors.
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PMID:Presynaptic gamma-aminobutyric acid receptors in the rat anococcygeus muscle and their antagonism by 5-aminovaleric acid. 628 54

The actions of gamma-aminobutyric acid (GABA) and its analogues, 3-amino-1-propanesulphonic acid (3APS) and baclofen, have been investigated using isolated segments of the guinea-pig ileum and distal colon. GABA and 3APS, but not baclofen, induced GABAA-receptor mediated effects; prompt, dose-dependent contractions of the ileum which were antagonised by bicuculline, picrotoxinin, piretanide, tetramethylenedisulphotetramine, atropine and tetrodotoxin. Baclofen and GABA, but not 3APS, induced a dose-dependent GABAB-receptor mediated depression of electrically elicited twitch contractions of the ileum, unaffected by the GABAA-receptor antagonists or by antagonism of adenosine, adrenergic, opiate or nicotinic receptors. In the distal colon, baclofen and GABA caused a bicuculline- and picrotoxinin-insensitive depression of spontaneous cholinergic contractions. Desensitization to GABA and baclofen, and cross-desensitization to both agonists was observed. Combined antagonism of GABAA-receptors and desensitization to baclofen slowed pellet expulsion to the same extent as GABA desensitization alone, indicating that both GABAA- and GABAB-receptor sites are involved in this modification of peristalsis by GABA.
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PMID:GABAA- and GABAB-receptor-mediated modification of intestinal motility. 629 29

Baclofen, commonly used to reduce severe muscle spasms in patients with spinal cord injuries, is also active in the brain. A patient with pre-existing bipolar affective disorder developed increased depression while on baclofen, which progressed to a delusional depression when baclofen and haloperidol were rapidly decreased. When the dose of haloperidol was increased to a previously well tolerated dose to deal with the depressive delusion, a pseudoparkinson's state developed. This case demonstrates the interactive effects of baclofen and haloperidol on central noradrenergic and dopaminergic systems and suggests a possible neurochemical basis for the difference between delusional and nondelusional depression that is consistent with the different therapeutic response to psychotropic drugs of patients with these illnesses. The paradoxical appearance of the pseudoparkinson state in this patient when much higher doses of haloperidol had been free of such side effects, may reflect baclofen-induced alterations in receptor sensitivity. It appears that baclofen should be used with caution in patients with neuropsychiatric problems and that, when used, the withdrawal of baclofen should be continued over several weeks to allow receptor sensitivity to return to normal levels.
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PMID:A possible neurochemical basis for the neuropsychiatric aspects of baclofen therapy. 632 74

Baclofen has been used as an antispastic agent for over a decade, yet its mechanism of action is still not fully understood. While early iontophoretic studies revealed a depression of neuronal activity, more recent studies have emphasized a presynaptic depression of transmitter release, both in the peripheral and central nervous system, possibly resulting from a blockade of calcium channels. Although baclofen is structurally similar to the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), none of its actions seem to be antagonized by the GABA antagonist, bicuculline. However, recent experiments have indicated that baclofen binds to a class of bicuculline-resistant GABA receptors, termed GABAB receptors. Here, we have analysed the action of baclofen on the membrane potential of CA1 hippocampal pyramidal cells in vitro and report that it directly hyperpolarizes these cells in a potent, stereoselective manner which is resistant to bicuculline methiodide. This response is associated with a decrease in neuronal input resistance and may involve an increase in potassium conductance.
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PMID:Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. 670 51

The participation of local anesthetic action in spinal reflex inhibition produced by mephenesin-type muscle relaxants was examined by comparing the local anesthetic effects (in vitro), the depressant effects on muscle afferent discharges (in situ) and the depressant effects on spinal reflexes (in situ) of the drugs in rats. At doses producing depression of spinal reflexes, mephenesin, tolperisone (mephenesin-type) and lidocaine (local anesthetic) reduced the frequency of afferent discharges from the muscle. The order of reducing afferent discharges by these drugs corresponded to that of their conduction blocking activities in the isolated sciatic nerve of rats. These results suggest the participation of a membrane stabilizing action in spinal reflex inhibition produced by mephenesin-type muscle relaxants. Baclofen (non-mephenesin-type) did not show any local anesthetic action.
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PMID:Mechanisms of depressant action of muscle relaxants on spinal reflexes: participation of membrane stabilizing action. 674 8


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