Cocaine: Clinical pharmacology and toxicology

Farrar, Henry C.; Kearns, Gregory L.

doi:10.1016/s0022-3476(89)80640-7

Cited by 102 publications

(39 citation statements)

References 95 publications

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“…Indeed, following rapid mucosal absorption (42), cocaine easily crosses the placental and the fetal blood-brain barriers (15), thanks to its small molecular weight, low degree of ionization at physiologic pH, weak protein binding, and high water and lipid solubility (43). Furthermore, the activity of esterases involved in cocaine degradation decreases in adult plasma during pregnancy and is very low in the fetus (44).…”

Section: Discussionmentioning

confidence: 99%

Selective neuronal toxicity of cocaine in embryonic mouse brain cocultures.

Nassogne¹,

Evrard²,

Courtoy³

1995

Proc. Natl. Acad. Sci. U.S.A.

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Cocaine exposure in utero causes severe alterations in the development of the central nervous system. To study the basis of these teratogenic effects in vitro, we have used cocultures of neurons and glial cells from mouse embryonic brain. Cocaine selectively affected embryonic neuronal cells, causing first a dramatic reduction of both number and length of neurites and then extensive neuronal death. Scanning electron microscopy demonstrated a shift from a multipolar neuronal pattern towards bi-and unipolarity prior to the rounding up and eventual disappearance of the neurons. Selective toxicity of cocaine on neurons was paralleled by a concomitant decrease of the culture content in microtubuleassociated protein 2 (MAP2), a neuronal marker measured by solid-phase immunoassay. These effects on neurons were reversible when cocaine was removed from the culture medium. In contrast, cocaine did not affect astroglial cells and their glial fibrillary acidic protein (GFAP) content. Thus, in embryonic neuronal-glial cell cocultures, cocaine induces major neurite perturbations followed by neuronal death without affecting the survival of glial cells. Provided similar neuronal alterations are produced in the developing human brain, they could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following in utero exposure to cocaine.

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Section: Discussionmentioning

confidence: 99%

Selective neuronal toxicity of cocaine in embryonic mouse brain cocultures.

Nassogne¹,

Evrard²,

Courtoy³

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…These cocaine concentrations range from innocuous to extremely toxic, based on human toxicology data (24)(25)(26). In the SFM experiments, media, and additives were changed daily.…”

Section: Methodsmentioning

confidence: 99%

Cocaine differentially inhibits neuronal differentiation and proliferation in vitro.

Zachor

Cherkes²,

Fay³

et al. 1994

J. Clin. Invest.

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The outcome of in utero cocaine exposure is unclear. To determine if cocaine affects neuronal growth and differentiation, we used PC-1 2 cells, which have a mitogenic response to IGF-I and differentiate into neurons on exposure to nerve growth factor. Differentiation was quantified as neurite extension after a 72-h exposure to 20 ng/ml nerve growth factor (dosage at 50% maximal effectiveness) and cocaine doses ranging from 0.01 to 10 gg/ml. The results were 49±2, 40±3, 29±2, 23±2, and 12±2% differentiation with respective cocaine concentrations of 0, 0.01, 0.1, 1, and 10 ,g/ml (P < 0.0001). Cocaine stability studies showed insignificant spontaneous hydrolysis under the conditions of this study. Cocaine did not affect cell viability or number, but had a relatively modest, statistically significant (P < 0.0001 ) inhibitory effect on IGF-I-stimulated thymidine incorporation. The dose-response curves for differentiation vs mitogenic response differed significantly (P = 0.021). Therefore, cocaine inhibition of these processes is probably mediated by different mechanisms, and not caused by generalized toxicity. To our knowledge, this is the first demonstration of cocaine effects on neuronal multiplication and differentiation in vitro. The results suggest in utero exposure may directly impair brain development. (J. Clin. Invest. 1994. 93:1179-1185

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“…The phenomenon of "cocaine abuse" by pregnant women received widespread media attention due to observations of serious, life-endangering consequences for the mother and fetus (Burkett et al, 1990;Critchley et al, 1988;Henderson and Torbey, 1988;Mercado et al, 1989;Morild and Stajic, 1990). Known catastrophic cardiovascular and central nervous system effects of cocaine use in adults (Cregler and Mark, 1986;Farrar and Kearns, 1989;Gawin and Ellinwood, 1988;Tarr and Macklin, 1987) clearly raised concerns that maternal use of cocaine, especially crack cocaine, would cause long-term, irreparable damage to the developing infant and young child. However, numerous limitations in study design among the earliest published studies on the effects of in utero cocaine exposure have been noted and results have been inconsistent for most aspects of infant and child developmental outcomes (Bandstra and Burkett, 1991;Carmichael Olson and Toth, 1999;Frank et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis

Bandstra

Vogel

Morrow

et al. 2004

Substance Use & Misuse

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The current study estimates the longitudinal effects of severity of prenatal cocaine exposure on language functioning in an urban sample of full-term African-American children (200 cocaineexposed, 176 noncocaine-exposed) through age 7 years. The Miami Prenatal Cocaine Study sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and toxicology assays of maternal and infant urine and infant meconium. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals-Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal latent growth curve analyses were used to examine two components of language functioning, a more stable aptitude for language performance and a time-varying trajectory of language development, across the three time points and their relationship to varying levels of prenatal cocaine exposure. Severity of prenatal cocaine exposure was characterized using a latent construct combining maternal self-report of cocaine use during pregnancy by trimesters and maternal and infant bioassays, allowing all available information to be taken into account. The association between severity of exposure and language functioning was examined within a model including factors for fetal growth, gestational age, and IQ as intercorrelated response variables and child's age, gender, and prenatal alcohol, tobacco, and marijuana exposure as covariates. Results indicated that greater severity of prenatal cocaine exposure was associated with greater deficits within the more stable aptitude for language performance (D = −0.071, 95% CI = −0.133, −0.009; p = 0.026). There was no relationship between severity of prenatal cocaine exposure and the time-varying trajectory of language development. The observed cocaineassociated deficit was independent of multiple alternative suspected sources of variation in language performance, including other potential responses to prenatal cocaine exposure, such as child's intellectual functioning, and other birth and postnatal influences, including language stimulation in the home environment.

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Cocaine: Clinical pharmacology and toxicology

Cited by 102 publications

References 95 publications

Selective neuronal toxicity of cocaine in embryonic mouse brain cocultures.

Selective neuronal toxicity of cocaine in embryonic mouse brain cocultures.

Cocaine differentially inhibits neuronal differentiation and proliferation in vitro.

Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis

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