Inhibition of Prolactin Secretion by Lergotrile Mesylate: Mechanism of Action

Ja, Clemens; Eb, Smalstig; Cj, Shaar

doi:10.1530/acta.0.0790230

Cited by 65 publications

(14 citation statements)

References 3 publications

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“…However, a similar P-induced interaction between NE system and LH-RH neurons occurring in the MBH can not yet be completely ruled out. With respect to the observation of inhibition cf prolactin release by LM our studies do not rule out the central effects of LM though it seems more likely that this effect was caused by stimulation of DA receptors on prolactin secreting cells in the pituitary (Clemens et al 1975). Furthermore, the findings that prolactin and gonadotrophins were simultaneously elevated and these surges were consistently blocked by DDC suggest that a common central NE system may mediate this stimulatory feedback action of the gonadal steroids.…”

Section: Discussioncontrasting

confidence: 63%

Effect of Norepinephrine Synthesis Inhibitors and a Dopamine Agonist on Hypothalamic Lh-Rh, Serum Gonadotrophin and Prolactin Levels in Gonadal Steroid Treated Rats

Kalra

Chen

et al. 1978

Acta Endocrinologica

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The relationship between the medial basal hypothalamus (MBH) LH-RH activity and LH release was studied following progesterone (P) treatment of oestrogen-primed ovariectomized rats (day 0). Following P administration at 10.00 h (day 2) serum LH levels increased rapidly after 13.00 h to peak levels attained at 15.00 h and maintained until 18.00 h. Coincident with the onset of augmented release and peak serum LH concentrations at 15.00 h there was a significant enhancement in the MBH LH-RH activity. Thereafter, the MBH LH-RH stores promptly fell and remained at morning low levels through the rest of the LH surge period. P treatment also stimulated release of FSH and prolactin in the afternoon. Administration of norepinephrine (NE) synthesis inhibitors, diethyldithiocarbamate (DDC) and U-14,624 before P blocked the afternoon increments in serum gonadotrophins and the MBH LH-RH levels; prolactin release was also suppressed in DDC treated rats. In contrast, lergotrile mesylate (dopamine agonist) treatment prior to P administration suppressed only the afternoon increase in prolactin release. These studies show that (1) P can stimulate MBH LH-RH activity in oestrogen-primed rats and these Supported by grant NIH HD 08634. 0 Eli Lily Research Laboratories, Indianapolis, Indiana. effects are transmitted to the LH-RH peptidergic neurons via NE synapses in the preoptic area and (2) a common central NE system may mediate the stimulatory feedback effects of P on gonadotrophin and prolactin release.Administration of progesterone ( ) to oestrogen-primed ovariectomized rats elicits a pro-oestrus-type surge of serum gonadotrophins (Caligaris et al. 1971; Kalra et al. 1972) and prolactin {Caligaris et al. 1974). Several studies have demonstrated that the stimulatory feedback action of on gonadotrophins is mediated primarily by central norepinephrine (NE) systems {Kalra et al. 1972; Kalra l'alia), however, the neurotransmitter(s) involved in prolactin release has not been identified. Besides these information, little is known about the neuro¬ endocrine mechanisms by which progesterone stimulates the secretion of pituitary gonadotrophins and prolactin. In this report we describe (a) the time sequence of changes in hypothalamic LH-RH activity associated with the Pinduced surge of serum LH and (b) the effects of two NE synthesis inhibitors, diethyldithiocarbamate (DDC, Magos 8c Jarvis 1970; Carr et al. 1977) and U-14,624 (l-phenyl-3-(2-thiazolyl)-2 thiourea, Johnson et al. 1970; Khalsa et al.

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Section: Discussioncontrasting

confidence: 63%

Effect of Norepinephrine Synthesis Inhibitors and a Dopamine Agonist on Hypothalamic Lh-Rh, Serum Gonadotrophin and Prolactin Levels in Gonadal Steroid Treated Rats

Kalra

Chen

et al. 1978

Acta Endocrinologica

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“…The reported effectiveness of lergotrile mesylate in the treatment of Parkinson's disease (Lieberman et al, 1975) probably depends on lergotrile's ability to stimulate dopamine receptors (Clemens et al, 1975), which in our studies in rats is manifest as a decrease in dopamine turnover and brain concentration of DOPAC.…”

Section: Discussionmentioning

confidence: 57%

Effect of lergotrile on3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain

Fuller

Perry

1978

J. Neural Transmission

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Lergotrile, a dopamine agonist, lowered whole brain DOPAC (3,4-dihydroxyphenylacetic acid) concentration in rats. At low doses down to 0.5 mg/kg of lergotrile mesylate, this effect occurred within 30 min, whereas at higher doses (20 mg/kg) the decline in DOPAC was delayed. The decrease in DOPAC persisted for several hours and presumably resulted from a compensatory decrease in brain dopamine turnover secondary to receptor stimulation by lergotrile. Other indications of decreased brain dopamine turnover after lergotrile included (a) a slower decline in dopamine concentration after synthesis inhibition by alpha-methyltyrosine, (b) a slower decline in alpha-methyl-m-tyramine, a false transmitter that is stored and released by dopamine neurons, and (c) a decreased accumulation of dopamine in response to gamma-butyrolactone, an agent that blocks firing and dopamine release by dopamine neurons. Lergotrile mesylate (20 mg/kg) also increased brain levels of 5-hydroxyindoleacetic acid and of 3-methoxy-4-hydroxyphenylethylene glycol sulfate, metabolites of serotonin and norepinephrine, respectively, and these increases were not antagonized by spiperone, a dopamine receptor antagonist.

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“…reversed the GBL-induced increase in DA concentrations in the striatum, nucleus accumbens and olfactory . Lergotrile has been shown to lower basal serum prolactin concentrations with a similar time course to that ofbromocriptine (Lemberger et al, 1974;Clemens et al, 1975;Thorner et al, 1978). The effect of lergotrile on the rate of DA synthesis in terminals of the nigrostriatal and mesolimbic DA systems in saline-and GBL-treated rats is presented in Fig.…”

Section: Resultsmentioning

confidence: 82%

Differential action of bromocriptine on nigrostriatal versus mesolimbic dopaminergic neurons

Barton

Moore

Demarest

1987

J. Neural Transmission

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The present study was undertaken to compare the abilities of the dopaminergic agonists apomorphine, bromocriptine, and lergotrile to inhibit the synthesis of dopamine (DA) in terminals of nigrostriatal and mesolimbic DA neurons. The in vivo synthesis of DA was estimated by measuring the rate of accumulation of dihydroxyphenylalanine (DOPA) in terminals of nigrostriatal (striatum) and mesolimbic (nucleus accumbens, olfactory tubercle) neurons 30 min after the administration of NSD 1015, a decarboxylase inhibitor. The activation of DA autoreceptors in these regions was evaluated by measuring the abilities of the DA agonists to inhibit DA synthesis in brain regions of rats pretreated with gamma-butyrolactone (GBL). Apomorphine (0.03-1.0 mg/kg for 45 min) and bromocriptine (0.1-10 mg/kg for 90 min) produced dose-dependent decreases in the rate of DA synthesis in all three brain regions of both vehicle- and GBL-treated rats. A time course of the effects of the highest dose of bromocriptine (10 mg/kg), however, demonstrated dramatic regional differences in the ability of this drug to inhibit DA synthesis in saline-versus GBL-pretreated rats. Bromocriptine inhibited the GBL-induced increase in DA synthesis for 6 hours in all regions examined. In the striatum of saline-treated rats the decrease in DA synthesis was evident only at 1.5 hours after bromocriptine administration, while in the nucleus accumbens and olfactory tubercle DA synthesis remained inhibited for 6 hours. By contrast, lergotrile reduced DA synthesis to a similar extent in all three regions for at least 6 hours in both vehicle- and GBL-treated rats. These results suggest that there is no regional difference in the ability of bromocriptine to inhibit DA synthesis via DA autoreceptor mechanisms, but there appear to be differences in postsynaptic DA receptor-mediated mechanisms which regulate nigrostriatal versus mesolimbic DA neurons.

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Inhibition of Prolactin Secretion by Lergotrile Mesylate: Mechanism of Action

Cited by 65 publications

References 3 publications

Effect of Norepinephrine Synthesis Inhibitors and a Dopamine Agonist on Hypothalamic Lh-Rh, Serum Gonadotrophin and Prolactin Levels in Gonadal Steroid Treated Rats

Effect of Norepinephrine Synthesis Inhibitors and a Dopamine Agonist on Hypothalamic Lh-Rh, Serum Gonadotrophin and Prolactin Levels in Gonadal Steroid Treated Rats

Effect of lergotrile on3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain

Differential action of bromocriptine on nigrostriatal versus mesolimbic dopaminergic neurons

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