Transfer of morphine across the human placenta and its interaction with naloxone

Kopecky, Ernest A.; Simone, Carmine; Knie, Brenda; Koren, Gideon

doi:10.1016/s0024-3205(99)00503-2

Cited by 39 publications

(31 citation statements)

References 23 publications

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“…naloxone) are effective treatments for fetal distress but they do not alter the maternal-to-fetal transfer rate of morphine. Thus, the antagonism of fetal distress by naloxone is explained by interactions with the fetal opiate receptors and not by the rate of transfer from mother to fetus [Vaccarino and Kastin, 2000;Kopecky et al, 1999]. Prenatal exposure to opiate antagonists in rats results in acceleration in both physical and behavioral maturation [McLaughlin et al, 1997b], including increased body weights and wet weights of brain, heart, kidney, lungs, liver and muscle groups [McLaughlin et al, 1997a].…”

Section: Discussionmentioning

confidence: 99%

Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses

Sandman¹,

Glynn²,

Wadhwa

et al. 2003

Dev Neurosci

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Maternal peptides from the hypothalamic-pituitary-adrenal (HPA) axis rise during human pregnancy. The effects of circulating maternal adrenocorticotropin (ACTH) and β-endorphin (BE) on human fetal behavior was determined in 135 women during their 32nd week of gestation. Fetal behavior was measured by assessing heart rate habituation to a series of repeated vibroacoustic stimuli. Individual differences in habituation were determined by computing the number of consecutive responses above the standard deviation during a control period. There was no significant relation between levels of ACTH, BE and the rate of fetal heart rate habituation. However, an index of HPA disregulation (uncoupling of ACTH and BE) was related significantly to fetal behavior. Fetal exposure to high levels of maternal BE relative to ACTH was associated with significantly lower rates of habituation. Results indicate that maternal stress and stress-related peptides influence fetal response patterns. It is possible that this influence persists over the life span.

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Section: Discussionmentioning

confidence: 99%

Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses

Sandman¹,

Glynn²,

Wadhwa

et al. 2003

Dev Neurosci

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“…Pregnant women are of higher importance among morphine abusers, since it has been demonstrated that morphine can easily transfer across the placenta, and its retention in placenta prolongs fetal exposure to morphine (Kopecky et al 1999). Furthermore, the existence of opioid receptors of µ, κ, and δ types has been confirmed in fetal tissues and placenta villi (Ahmed et al 1989;Leslie et al 1998;Ray and Wadhwa 1999).…”

Section: Introductionmentioning

confidence: 99%

Maternal Oral Consumption of Morphine Increases Bax/Bcl-2 Ratio and Caspase 3 Activity During Early Neural System Development in Rat Embryos

et al. 2009

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Maternal morphine consumption has been shown to result in physical and neurobehavioral defects in fetus and offspring, but the underlying molecular mechanisms of these defects remain unclear. Regarding the critical role of apoptosis in normal development of central nervous system, the present study was designed to investigate the effect of intrauterine morphine exposure on programmed cell death of neuroblasts during the early development of neural system. Pregnant Wistar rats received morphine sulfate through drinking water at the concentration of 0.01 mg/ml (20 ml water per day for each rat) from the first day of gestation to the time of sampling. Control groups received tap water. Control and morphine-treated pregnant rats, each in five separated groups, were killed on gestational days 9.5 to 13.5, and the embryos were taken out, fixed, and embedded in paraffin. Immunohistochemical assay was used to reveal the protein expression of Bax, Bcl2, and the activation of caspase 3. The results showed a significant increase in Bax immunoreactivity in all of the mentioned embryonic days (E9.5 to E13.5) and a significant decrease in Bcl-2 immunoreactivity at days E10.5 and E12.5 in morphine-treated groups compared with control. Data analysis revealed that Bax/Bcl2 ratio was increased in all of the morphine-exposed groups. Consistent with these results, immunostaining of cleaved caspase 3 showed a significant increase at days E11.5 to E13.5. These findings suggest that morphine exposure during the first embryonic days may enhance the susceptibility of neuroblasts to apoptosis by upregulating the ratio of Bax to Bcl-2 protein expression and increasing downstream caspase-3 activity. The increased probability of neuroblast apoptosis may be the cause of morphine-induced defects in the central nervous system development and its structural and neurobehavioral consequences.

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“…Maternal morphine readily crosses the term placenta with a transfer rate in the region of 0.73 ngAEmL À1 min À1 . 2 Her baby was small at 2.75 kg possibly increasing its susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Opioid-related narcosis in a woman with myopathy receiving magnesium

Robins

Lyons

2007

International Journal of Obstetric Anesthesia

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Transfer of morphine across the human placenta and its interaction with naloxone

Cited by 39 publications

References 23 publications

Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses

Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses

Maternal Oral Consumption of Morphine Increases Bax/Bcl-2 Ratio and Caspase 3 Activity During Early Neural System Development in Rat Embryos

Opioid-related narcosis in a woman with myopathy receiving magnesium

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