Comparison of the behavioral effects of gamma-hydroxybutyric acid (GHB) and its 4-methyl-substituted analog, gamma-hydroxyvaleric acid (GHV).
Gamma-hydroxybutyrate (GHB), a metabolite of GABA, is a drug of abuse and a therapeutic. The illicit use of GHB precursors and analogs reportedly has increased worldwide. Gamma-hydroxyvaleric (GHV) is a 4-methyl-substituted analog of GHB that reportedly is abused and is marketed as a dietary supplement and replacement for GHB. The purpose of these studies was to compare the pharmacological and behavioral profiles of GHV and GHB. In radioligand binding studies, GHV completely displaced [(3)H]NCS-382 with approximately 2-fold lower affinity than GHB and did not markedly displace [(3)H]GABA from GABA(B) receptors at a 20-fold larger concentration. In drug discrimination procedures, GHV did not share discriminative stimulus effects with GHB or baclofen. GHV shared other behavioral effects with GHB, such as sedation, catalepsy, and ataxia, although larger doses of GHV were required to produce these effects. Lethality (50%) was observed after the largest dose of GHV (5600mg/kg), a dose that produced less-than-maximal catalepsy and ataxia. To the extent that large doses of GHV might be taken to in an attempt to produce GHB-like effects (e.g., hypnosis) GHV toxicity may pose a greater public health concern than GHB.
Carter
Lawrence P
LP
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Code 7764, San Antonio, TX 78229-3900, USA.
Chen
Weibin
W
Wu
Huifang
H
Mehta
Ashok K
AK
Hernandez
R Jason
RJ
Ticku
Maharaj K
MK
Coop
Andrew
A
Koek
Wouter
W
France
Charles P
CP
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006885:Hydroxybutyrates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010421:Pentanoic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology
D006885:Hydroxybutyrates; D010421:Pentanoic Acids; C111420:4-hydroxybutyric acid; C038780:n-pentanoic acid