Progesterone “Anesthesia” in Human Subjects

Merryman, W. David; Boiman, Richard E.; Barnes, Lloyd; Rothchild, I.

doi:10.1210/jcem-14-12-1567

Cited by 135 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Progesterone and progesterone-derived neurosteroids are endogenous neuromodulators with sedative, anxiolytic, and anesthetic activity (1)(2)(3)(4)(5)(6). However, the molecular mechanisms underlying the central nervous system effects of progesterone remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Differential anesthetic activity of ketamine and the GABAergic neurosteroid allopregnanolone in mice lacking progesterone receptor A and B subtypes

Reddy¹,

Zeng²

2007

Methods and Findings in Experimental and Clinical Pharmacology

View full text Add to dashboard Cite

SUMMARY-Progesterone affects the function of the brain by multiple mechanisms. The physiological effects of progesterone are mediated by interaction of the hormone with progesterone receptors (PRs), which are widely expressed in the hypothalamus, hippocampus and limbic areas. The PR is composed of two protein isoforms, PR-A and PR-B, which are expressed from a single PR gene. In addition, progesterone influences neuronal activity through its conversion to allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of GABA A receptors. However, the role of PRs in the sedative-hypnotic action of neurosteroids is unclear. In this study, PR knockout (PRKO) mice were used as model to study the sedative-anesthetic actions of the progesterone-derived neurosteroid allopregnanolone and the non-competitive NMDA receptor antagonist ketamine. Mice were confirmed to be PR deficient by genotyping and immunohistochemistry of PR expression in the brain. Anesthetic potency was evaluated by the loss of the righting reflex paradigm. Allopregnanolone induced anesthetic activity was similar in PRKO mice and their wild-type littermates, suggesting that PRs are not involved in the anesthetic response to allopregnanolone. However, the non-competitive NMDA receptor antagonist ketamine has significantly reduced anesthetic potency in PRKO mice, suggesting a possible developmental plasticity of glutamate receptors. There was no marked gender-related difference to ketamine response in both genotypes. In conclusion, these results suggest that the neurosteroid allopregnanolone and ketamine produce differential anesthetic response in mice lacking PRs.

show abstract

Section: Introductionmentioning

confidence: 99%

Differential anesthetic activity of ketamine and the GABAergic neurosteroid allopregnanolone in mice lacking progesterone receptor A and B subtypes

Reddy¹,

Zeng²

2007

Methods and Findings in Experimental and Clinical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Administration of progesterone in various mammalian species has revealed analgesic, anxiolytic and sleep modulating e¤ects (Kavaliers and Wiebe 1987;Bitran et al 1993Bitran et al , 1995Lancel et al 1996). In humans, hypnotic (Merryman et al 1954), sleep modulating (Friess et al 1997) and anticonvulsant actions (Bäckström et al 1984) have been found after intravenous or oral administration of progesterone. Some of the central nervous e¤ects of progesterone have been attributed in part to the conversion of progesterone into neuroactive steroids that allosterically modulate the GABA A receptor (Paul and Purdy 1992;Lambert et al 1995;Rupprecht 1997).…”

Section: Introductionmentioning

confidence: 99%

Assessment of neuroleptic-like properties of progesterone

et al. 1999

View full text Add to dashboard Cite

There is considerable evidence from epidemiological studies that the onset of psychiatric disorders may be related to changes in the secretion of gonadal hormones. For example, the postpartum period appears to be a vulnerable phase for the occurrence of psychiatric disturbances such as dysphoric mood and even severe psychotic disturbances. It has been suggested that a sudden drop in progesterone concentrations may contribute to the development of such disorders. Because the administration of this steroid might be of therapeutic value in psychiatric disturbances, we investigated the behavioral properties of progesterone in the rat to assess putative neuroleptic-like properties of this steroid. Progesterone administration dose-dependently increased the EEG activity during wakefulness in the 10- to 30-Hz frequency bands and decreased locomotor activity. While no anxiolytic activity could be detected in the plus maze, the highest dose of progesterone (90 mg/kg) exerted an inhibitory effect on the conditioned avoidance response. In contrast to haloperidol (0.5 mg/kg), progesterone neither produced catalepsy nor antagonized amphetamine-induced stereotypy. However, both progesterone (10, 30 and 90 mg/kg) and haloperidol (0.1 mg/kg) effectively restored the disruption of the prepulse inhibition (PPI) of the acoustic startle response (ASR) that was evoked by apomorphine (2 mg/kg). In contrast, allopregnanolone (10 mg/kg), one of the main metabolites of progesterone, did not significantly antagonize the effect of apomorphine on the PPI. This behavioral profile of progesterone is compatible with the sedative properties of its metabolite allopregnanolone via the GABAA receptor, but also with the possibility that progesterone itself shares some properties with atypical antipsychotics, which may be relevant for the development and treatment of psychotic disturbances.

show abstract

“…Administration of exogenous progesterone in various mammalian species revealed analgesic and anxiolytic ef fects [4][5][6], In humans, hypnotic [7] and anticonvulsant K A R G F R. properties [8] have been shown following intravenous administration of progesterone. Studies in female subjects using an oral administration route reported a transient fatigue and a decrease of information processing and of verbal memory function [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Assessment of Cognitive Performance after Progesterone Administration in Healthy Male Volunteers

Grön

Frieß

Herpers³

et al. 1997

Neuropsychobiology

View full text Add to dashboard Cite

Administration of progesterone produces sleep EEG patterns that resemble those of agonistic modulators at the GABA_A receptor. Previous studies evaluating the effects of an oral progesterone administration on attention performance in females pointed to putative sedative effects of progesterone at high dosages. However, no data are available whether progesterone dosages that influence sleep produce sedative hangover effects on the following morning. Therefore, we assessed the effects of a single oral dose of 300 mg micronized progesterone administered in the evening on cognitive performance parameters in male healthy volunteers on the following morning using a placebo-controlled double-blind crossover design. There was a great variability in bioavailability following progesterone intake. The administration of progesterone produced no consistent effects on attention performance. Thus, dosages of progesterone that are sufficient to modulate sleep are not likely to exert sedative hangover effects.

show abstract

Progesterone “Anesthesia” in Human Subjects

Cited by 135 publications

References 0 publications

Differential anesthetic activity of ketamine and the GABAergic neurosteroid allopregnanolone in mice lacking progesterone receptor A and B subtypes

Differential anesthetic activity of ketamine and the GABAergic neurosteroid allopregnanolone in mice lacking progesterone receptor A and B subtypes

Assessment of neuroleptic-like properties of progesterone

Assessment of Cognitive Performance after Progesterone Administration in Healthy Male Volunteers

Contact Info

Product

Resources

About