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)

Intravenous administration of increasing doses of the ergoline, lergotrile mesylate, caused a rapid, dose-dependent and haloperidol-reversible inhibition of unit activity of dopamine cells in the pars compacta of the rat substantia nigra. 6 microgram/kg caused significant depression of dopamine cell firing rates; 50% inhibition was achieved with a cumulative dose of 100 microgram/kg. 60% of the cells were completely inhibited by increasing doses of the drug, the remainder became resistant to further inhibition after reaching rates 25--50% of baseline. Pretreatment with reserpine and alpha-methylparatyrosine did not significantly attenuate the lergotrile-induced inhibition. Lergotrile had no consistent effect on firing rates of cells in the pars reticulata of the substantia nigra. The ergoline reduced the apparent activation of striatal dopamine synthesis associated with complete cessation of impulse flow in nigral-striatal dopamine neurons induced by gamma-butyrolactone treatment. These effects are compared with those of apomorphine and amphetamine. The results are consistent with the idea that lergotrile is a direct acting dopamine agonist.
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PMID:Dopamine neurons: effect of lergotrile on unit activity and transmitter synthesis. 4 59

The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.
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PMID:Effect of the dopamine agonist, lergotrile mesylate, on circulating anterior pituitary hormones in man. 4 63