Mechanisms Underlying the Sympathomimetic Cardiovascular Responses Elicited by γ-Hydroxybutyrate

Hicks, Alissa R.; Kapusta, Daniel R.; Varner, Kurt J.

doi:10.1097/00005344-200412000-00002

Cited by 19 publications

(12 citation statements)

References 33 publications

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“…Furthermore, following GHB intoxication hypotension is frequently reported 10 . However, recent results suggest that GHB has also sympathomimetic cardiovascular effects that could induce increases in blood pressure following its acute administratrion 38 . Further studies with a larger population of subjects are needed to confirm these findings.…”

Section: Discussionmentioning

confidence: 99%

γ‐Hydroxybutyrate (GHB) in Humans

Abanades

Farré

Segura

et al. 2006

Annals of the New York Academy of Sciences

111

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Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.

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Section: Discussionmentioning

confidence: 99%

γ‐Hydroxybutyrate (GHB) in Humans

Abanades

Farré

Segura

et al. 2006

Annals of the New York Academy of Sciences

111

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“…Several other studies have shown that GHB and GHB precursors increase mean arterial pressure, heart rate (560–1,000 mg/kg, iv), and gastric emptying (100–300 mg/kg, ip or po) in rodents, and that these effects are mediated by GABA B receptors (Poggioli et al, 1999; Carai et al, 2002; Gerak et al, 2004; Hicks et al, 2004). Many studies, some of which are described below, have also implicated GABA B receptors as the primary mechanism mediating the hypnotic and anesthetic effects of GHB.…”

Section: Behavioral Effects Of Ghbmentioning

confidence: 99%

“…In addition to discriminative stimulus effects, GABA B receptor antagonists have also been shown to attenuate GHB-induced changes in brain activity, neurotransmitter release (Snead, 1996; Erhardt et al, 1998; Tremblay et al, 1998), mean arterial pressure, heart rate (Gerak et al, 2004; Hicks et al, 2004), gastric emptying (Carai et al, 2002), body temperature, locomotion, (Kaupmann et al, 2003; Quéva et al, 2003), catalepsy (Koek et al, 2007b), operant responding (Cook et al, 2002; Carter et al, 2004b; Goodwin et al, 2005), ataxia, and loss of righting (Carai et al, 2001; Cook et al, 2002; Carter et al, 2005b;Werawattanachai et al, 2007).…”

Section: Summary and Future Directionsmentioning

confidence: 99%

Behavioral analyses of GHB: Receptor mechanisms

Carter

Koek

France

2009

Pharmacology & Therapeutics

137

110

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GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABA B receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABA B receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABA A and GABA B receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects.

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“…The decreased bioavailability of GHB following enteral administration is not surprising given the drug is most likely susceptible to first pass metabolism in the liver (13). The MAP increasing effect of parenterally administered GHB has been shown to be mediated via the activation of central GABA b receptors; however, the ability of parenterally administered GHB to elicit increases in heart rate have been attributed to the its' ability to selectively inhibit baroreceptor reflex control of heart rate via the activation of specific GHB receptors (2). Given that the intragastric administration of GHB did not elicit dose-dependent, parallel increases in heart rate at doses which increased MAP, it is possible that the enteral absorption of GHB alters the affinity of the compound for the GHB receptor without altering GHB's affinity for GABA b receptors.…”

Section: Discussionmentioning

confidence: 99%

“…An endogenous compound metabolically linked to gamma aminobutyric acid, GHB is considered a CNS depressant; however, GHB also has significant sympathomimetic cardiovascular properties when administered parenterally (2)(3)(4). Accompanying the increased recreational use of GHB has been an increase in drug-related toxicity.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Responses Elicited by Intragastric Administration of BDL and GHB

Hicks

Varner

2008

Journal of Receptors and Signal Transduction

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Gamma-hydroxybutyrate (GHB) and its metabolic precursor, 1,4-butanediol (BDL) are widely used recreational drugs. Although most commonly described as CNS depressants, GHB and BDL elicit significant sympathomimetic cardiovascular responses (increases in mean arterial pressure (MAP) and heart rate) when administered parenterally. Given that humans most commonly ingest both drugs orally, we examined the dose-response relationships for intragastrically administered GHB and BDL on MAP and heart rate in conscious rats using radiotelemetry. The intragastric administration of GHB increased MAP. BDL increased both MAP and heart rate, and was approximately 10-fold more potent as a cardiovascular stimulant than GHB when administered intragastrically. Pretreatment with ethanol prevented the lethality of BDL. These data indicate that 1) both GHB and BDL produce cardiovascular responses when administered intragastrically, and 2) BDL is more potent and potentially more dangerous than GHB when administered via this route.

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Mechanisms Underlying the Sympathomimetic Cardiovascular Responses Elicited by γ-Hydroxybutyrate

Cited by 19 publications

References 33 publications

γ‐Hydroxybutyrate (GHB) in Humans

γ‐Hydroxybutyrate (GHB) in Humans

Behavioral analyses of GHB: Receptor mechanisms

Cardiovascular Responses Elicited by Intragastric Administration of BDL and GHB

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