Evaluation of the Abuse Potential of Pagoclone, a Partial GABAA Agonist

Abstract

This study assessed the abuse potential of pagoclone, a partial agonist at the gamma-aminobutyric acid type A (GABAA) benzodiazepine receptor site, in healthy recreational drug users. Twenty-three young adults, who reported past recreational use of sedative drugs or alcohol, participated in 4 sessions during which capsules containing pagoclone (doses: 1.2 mg, the higher end of the proposed therapeutic dose range, and 4.8 mg, a 4-fold higher dose), diazepam (dose, 30 mg), or placebo were randomly administered under double-blind conditions. Subjective ratings of mood, drug effects, and psychomotor tests were completed at regular intervals after ingesting the capsules. On most of the standardized measures of abuse potential, pagoclone (dose, 4.8 mg) was rated as being similar to diazepam. Both drugs increased the ratings of good effects and drug liking. However, pagoclone also produced some adverse mood effects that might limit its potential to be used recreationally, and it produced fewer sedativelike effects on some measures. In general, the results with these doses indicate that the abuse potential of pagoclone is similar to that of diazepam, although its profile as a partial agonist suggests that differences between the drugs may emerge at higher doses.

Reactions of 3-Hydroxy-2-phenyl-1H-benzo[e]isoindol-1-one: A Route to 3-Hydroxy-/3-anilinobenzo[e]indan-1-ones and Benzo[f]phthalazin-1(2H)-ones

“…The isoindolinone framework is present as the core unit in many synthetic and naturally occurring derivatives with interesting biological properties [ 1 , 2 , 3 ]. The ones commonly known are the hypotensive and inhibitory platelet aggregation activity of the nonbenzodiazepine sedative and hypnotic drug JM-1232 ( I , Figure 1 ) [ 4 , 5 , 6 ] as well as the anxiolytic agents Pagoclone ( II ) [ 7 ] and Staurosporine ( III ) [ 8 ]. Additionally, cytotoxicity activity against the HCT-116 human colon cancer cell line of the naturally occurring Chlorizidine A ( IV ) [ 9 ] was found.…”

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

“…A randomized double-blind study of patients suffering from panic attacks found that this compound provides anxiolytic effects without the typical side effects associated with BZDs (Sandford et al, 2001), but it has not been approved for use in the treatment of anxiety disorders (Bateson, 2003;Atack et al, 2006a;de Wit et al, 2006).…”

3-[1-(4-Methylphenyl)-3-oxo-1,3,4,5,6,7-hexahydro-2H-isoindol-2-yl]propanoic Acid

“…Several isoindolone derivatives have a range of biological activities including anti-inflammatory (indoprofen) [1], antiarrhytmic (ubisindine) [2,3], nootropic [4], anxiolytic and sedative (pazinaclone and pagoclone) [5,6] or diuretic and antihypertensive activity (chlorthalidone) [7]. Other derivatives have potent 5-HT 1A and 5-HT 2c receptor antagonist [8,9], antispasmodic [10], antinociceptive (JM-1232) [11] and hypnotic activity [12] while N,N-phthaloyl derivative of α-, β-and γ-amino acids showed anticonvulsant activity [13].…”