Behavioral comparisons of R-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane (BL-3912A) with R-DOM and S-Amphetamine

Abstract

The behavioral effects of R-2-amino-1-(2,5-dimethoxy-4-methylphenyl) butane or BL-3912A were compared with those of S-Amphetamine and R-DOM. BL-3912A facilitated acquisition of shuttle box responding by rats without increasing noncontingent intertrial (ITI) activity, while S-Amphetamine increased both avoidance and ITI responding. R-DOM had a biphasic effect on avoidance responding, increasing it at low doses and disrupting at higher doses. At doses that facilitated shuttle box responding, BL-3912A had no effect on unacclimated motor activity of rats nor on the rate of continuous avoidance responding by rats. S-Amphetamine increased the frequency of both motor activity and operant avoidance responding, while R-DOM decreased motor activity and increased operant avoidance responding. By facilitating avoidance behavior without increasing othermeasures of psychomotor activity, BL-3912A represents a unique psychopharmacological agent clearly different from R-DOM and S-Amphetamine.

Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs

“…The HTR of ( R )-Ariadne and ( rac )-4C-TFM was completely inhibited by MDL100,907 (volinanserin), a potent 5-HT 2A receptor antagonist, demonstrating that the attenuated HTR of the Ariadne compound class is driven by 5-HT 2A activation in vivo (Figures E and S12). General locomotion in response to a novel environment (open field test, OF) showed a minor sedative effect at the peak HTR dose of ( R )-Ariadne (10 mg/kg, s.c.) and a marked sedation at 30 mg/kg, consistent with previous studies in rats (Figure G) . DOPR showed minor to no effects on locomotion, trending toward an increased locomotion at its HTR peak dose (1 mg/kg), also consistent with minor stimulatory effects of phenylalkylamine psychedelics in mice (Figure H).…”

“…11 Ariadne also showed a lack of stimulant effects compared to (S)-amphetamine, exhibiting a distinct behavioral profile from that of classic hallucinogens and psychostimulants in rats and conscious beagle dogs. 12,13 In the same dose range (10 mg/kg, s.c. or i.p. ), (R)-Ariadne improved avoidance behavior in the absence of stimulant-like effects in rats.…”

Strategy for the assessment of neurobehavioral consequences of environmental factors.

“…The capability of rats to acquire an avoidance response in the shuttle box is a standard psychopharmacological test of learning and memory in the rat. The subjects will be dosed for 45 days and then given 120 massed acquisition trials in the shuttle box (34). The same subjects will be retested in an identical fashion at 90 days of dosing.…”

“…Since behavior is not under the control of external stimuli, it should be sensitive to changes in central nervous system (CNS) function (35). Rats will be trained to postpone electric footshock on an unsignalled continuous schedule (34). Training sessions will occur daily until a stable baseline of responding has been established.…”

Synthesis and biological evaluation of novel pyrimidine nucleoside analogs of 1,4-oxathiane, 1,4-dithiane, and 1,4-dioxane

“…The values for the substituent constants in Table I were taken from our recent compilation.14 Collinearity of Variables. The following squared correlation matrix shows that there is little collinearity among the variables used to formulate eq [1][2][3][4][5][6][7][8].…”