Pharmacological mechanisms in cocaine's cardiovascular effects

Schindler, Charles W.; Tella, Srihari R.; Erzouki, Hashim K.; Goldberg, Steven R.

doi:10.1016/0376-8716(94)01083-w

Cited by 48 publications

(9 citation statements)

References 44 publications

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“…2). In addition, while norcocaine is known to possess pharmacological activity and can produce cardiovascular effects of its own (Schindler et al 1995;Mahlakaarto et al 1998), the data reveal that norcocaine concentrations were barely above the level of detection during the second wash-out session.…”

Section: Direct Effects Of Oral Cocaine Maintenancementioning

confidence: 55%

Modulation of intravenous cocaine effects by chronic oral cocaine in humans

2000

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Section: Direct Effects Of Oral Cocaine Maintenancementioning

confidence: 55%

Modulation of intravenous cocaine effects by chronic oral cocaine in humans

2000

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“…While the precise mechanism by which cocaine affects cardiovascular parameters is not fully understood, there is evidence that adrenaline and noradrenaline are involved in cocaine pressor and tachycardiac effects, respectively (Schindler et al 1995). In this respect, it is important to note that selegiline treatment was associated with a small (30%) but significant reduction in MHPG levels.…”

Section: Discussionmentioning

confidence: 98%

Transdermal selegiline and intravenous cocaine: safety and interactions

et al. 2003

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“…5 The sympathomimetic and the local anesthetic effects of cocaine can lead to opposite effects on the cardiovascular functions, which is responsible for the large variability in the cardiovascular effects of cocaine. 6,7 Concurrent cocaine and alcohol use is one of the most frequently abused drug combinations. 8 The popularity of this drug combination arises primarily from the fact that abusers of this drug combination experience more intense and longer lasting euphoric effects, while the unpleasant disphoria experienced with cessation of cocaine use is reduced.…”

Section: Introductionmentioning

confidence: 99%

Cocaine and alcohol interactions in the rat: Effect on cocaine pharmacokinetics and pharmacodynamics

Pan

Hedaya

1999

Journal of Pharmaceutical Sciences

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The effect of alcohol coadministration on cocaine pharmacokinetics and pharmacodynamics was investigated in awake, freely moving rats. Cocaine plasma and brain extracellular fluid (ECF) concentration-time profiles were characterized after intraperitoneal (ip) administration of 30 mg/kg cocaine to rats that were pretreated with either normal saline or alcohol at 5 g/kg in a balanced crossover experimental design. The neurochemical response to cocaine administration, measured as the change in dopamine concentration in the nucleus accumbens (N ACC) and the change in the mean arterial blood pressure were monitored simultaneously. Intragastric alcohol administration significantly increased cocaine systemic bioavailability after ip administration from 0.550 +/- 0.044 to 0. 754 +/- 0.071. Also, the absorption rate constant increased from 0. 199 +/- 0.045 to 0.276 +/- 0.059 min-1 due to alcohol coadministration; however, this increase was not significant. Alcohol inhibition of cocaine metabolism caused an increase in cocaine elimination half-life from 26.3 +/- 3.6 to 40.0 +/- 8.1 min. Also, cocaine tissue distribution was enhanced by alcohol, resulting in a significant increase in cocaine volume of distribution. Analysis of the brain cocaine concentration-neurochemical effect relationship by the sigmoid-Emax pharmacodynamic model showed that Emax increased from 850 +/- 200 to 1550 +/- 640% of baseline due to alcohol coadministration, whereas EC50 decreased from 3400 +/- 580 to 2000 +/- 650 ng/mL, indicating higher cocaine potency in the presence of alcohol. The estimates of the indirect inhibitory pharmacodynamic model used to examine the plasma cocaine concentration-change in blood pressure relationship were not significantly different after the two treatments. These results indicate that alcohol significantly alters cocaine absorption, distribution, and elimination, resulting in higher and prolonged cocaine plasma concentration. Alcohol coadministration also potentiates the neurochemical response to cocaine administration.

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Pharmacological mechanisms in cocaine's cardiovascular effects

Cited by 48 publications

References 44 publications

Modulation of intravenous cocaine effects by chronic oral cocaine in humans

Modulation of intravenous cocaine effects by chronic oral cocaine in humans

Transdermal selegiline and intravenous cocaine: safety and interactions

Cocaine and alcohol interactions in the rat: Effect on cocaine pharmacokinetics and pharmacodynamics

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