Behavioral effects of the putative anxiolytic (±)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice

Scorza, Ma.Cecilia; Reyes‐Parada, Miguel; Silveira, Ricardo dos Reis; Viola, Haydeé; Medina, Jorge H.; Viana, Milena de Barros; Zangrossi, Hélio; Graeff, Frederico Guilherme

doi:10.1016/0091-3057(95)02149-3

Cited by 15 publications

(14 citation statements)

References 18 publications

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“…We have recently shown that (_+)l-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a phenethylamine derivative which has been reported to have psychedelic effects in humans (Shulgin and Shulgin 1991), exhibits an anxiolytic-like profile in mice and rats in the elevated plus maze test as well as in the elevated T-maze test (Scorza et al 1996).…”

Section: Introductionmentioning

confidence: 99%

(�)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors

Reyes‐Parada

Scorza

Romero

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (+/-)1-(2,5-dimethoxy-4-ethylthio-phenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki = 173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA receptors, the affinity was micromolar of lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.

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Section: Introductionmentioning

confidence: 99%

(�)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors

Reyes‐Parada

Scorza

Romero

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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“…13.7 ± 1.6 42.9 ± 3.6 54.7 ± 6.6 107.2 ± 7.9 PTMB (10) 11.3 ± 1.8 37.3 ± 2.8 43.8 ± 3.6 103.7 ± 8.9 PTMB (30) 9.7 ± 1.8* 39.0 ± 3.4 44.4 ± 5.3 116.6 ± 11.0 cific motor activity in rodents (5,11,13). In the holeboard, 2 mg/kg picrotoxin significantly decreased the number of head dips, the time spent head dipping, the number of rearing responses and the number of squares crossed with all paws.…”

Section: Picrotoxinmentioning

confidence: 99%

“…The holeboard test has been claimed to be suitable to assess directed exploratory behavior, since it allows the discrimination between exploratory activity and nonspe- cific motor activity in rodents (5,11,13). In the holeboard, 2 mg/kg picrotoxin significantly decreased the number of head dips, the time spent head dipping, the number of rearing responses and the number of squares crossed with all paws.…”

mentioning

confidence: 99%

“…Statistical analysis of the latency to fall from the rotarod revealed that diazepam (1 mg/kg) and PTMB (3, 10 and 30 mg/kg) produced significant motor incoordination compared to vehicle control (F(4,70) = 7.6; P<0.001; Figure 2). The holeboard test has been claimed to be suitable to assess directed exploratory behavior, since it allows the discrimination between exploratory activity and nonspe- 10.1 ± 2.5 36.8 ± 3.6 42.6 ± 6.5 158.7 ± 16.8* Vehicle 16.4 ± 2.2 40.9 ± 2.9 45.6 ± 2.5 107.9 ± 11.6 PTMB (0.3) 17.5 ± 3.0 38.7 ± 2.3 42.0 ± 3.5 106.1 ± 9.6 PTMB (1.0)18.4 ± 2.3 43.0 ± 2.8 51.1 ± 3.6 105.4 ± 10.5 PTMB (3.0)13.7 ± 1.6 42.9 ± 3.6 54.7 ± 6.6 107.2 ± 7.9 PTMB (10) 11.3 ± 1.8 37.3 ± 2.8 43.8 ± 3.6 103.7 ± 8.9 PTMB (30) 9.7 ± 1.8* 39.0 ± 3.4 44.4 ± 5.3 116.6 ± 11.0 cific motor activity in rodents (5,11,13). In the holeboard, 2 mg/kg picrotoxin significantly decreased the number of head dips, the time spent head dipping, the number of rearing responses and the number of squares crossed with all paws.…”

mentioning

confidence: 99%

“…search laboratories in the past 6 years (14-16) and has been extensively validated for use with both rats (2,15) and mice (1,11,13,17). The conventional indices of anxiety in this test, percent of open arm entries and percent time spent in the open arm, are exquisitely sensitive to agents thought to act via the GABA A receptor complex (i.e., benzodiazepines, barbiturates, ethanol, and neurosteroids) (14,17).…”

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confidence: 99%

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Anxiolytic-like effects of 4-phenyl-2-trichloromethyl-3H-1,5-benzodiazepine hydrogen sulfate in mice

Rubin

Albach

Berlese

et al. 2000

Braz J Med Biol Res

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The pharmacological effects of 4-phenyl-2-trichloromethyl-3H-1,5-benzodiazepine hydrogen sulfate (PTMB), a novel synthetic benzodiazepine, were examined in mice. In the elevated plus-maze test of anxiety, 0.3-1 mg/kg diazepam ip (F(3,53) = 3.78; P<0.05) and 1-10 mg/kg PTMB ip increased (F(5,98) = 3.26; P<0.01), whereas 2 mg/kg picrotoxin ip decreased (F(3,59) = 8.32; P<0.001) the proportion of time spent in the open arms, consistent with an anxiolytic action of both benzodiazepines, and an anxiogenic role for picrotoxin. In the holeboard, 1.0 mg/kg diazepam ip increased (F(3,54) = 2.78; P<0.05) and 2 mg/kg picrotoxin ip decreased (F(3,59) = 4.69; P<0.01) locomotor activity. Rotarod assessment revealed that 1 mg/kg diazepam ip and 3, 10 and 30 mg/kg PTMB ip produced significant motor incoordination compared to vehicle control (F(4,70) = 7.6; P<0.001). These data suggest that the recently synthesized PTMB compound possesses anxiolytic activity and produces motor incoordination similar to those observed with diazepam. PicrotoxinBenzodiazepine compounds have been reported to be the most extensively consumed psychoactive drugs worldwide due to their anxiolytic and anticonvulsant activity. However, undesirable side effects like muscle relaxation, sedation, physical dependence, tolerance, ataxia and memory impairment have been associated with the use of benzodiazepines. A variety of novel agents capable of interacting with benzodiazepine receptors have been investigated in order to develop non-sedative anxioselective agents (1-3). Two main hypotheses for the development of such anxioselective drugs have been proposed. The first suggests that different benzodiazepine receptor subtypes may be responsible for the behavioral effects of benzodiazepine compounds. According to this hypothesis, two receptor subtypes, benzodiazepine (omega) 1 and benzodiazepine (omega) 2 receptors, exist in different brain areas responsible for different physiological functions (2). The alternative hypothesis proposes the development of benzodiazepine receptor partial agonists which present lower intrinsic efficacy sufficient to maintain the anxiolytic and anticonvulsant responses, but insufficient to induce the side effects seen with full agonists (2,4). Most of the benzodiazepines used in clinical therapeutics are 1,4-benzodiazepines (5-7), since several products were generated by introducing substituents at different positions of the benzodiazepine ring of diazepam. Modifications in the structure of the ring have also been made, and the anxiolytic effect of 1,5-benzodiazepines (clobazam) has been described (8,9). However, considerably less is known about the effects of substituents on 1,5-benzodiazepines compared to the 1,4 group. In the present study we investigated the anxiolytic potential of the recently synthesized 4-phenyl-2-trichloromethyl-3H-1,5-benzodiazepine hydrogen sulfate (PTMB) (10). The effects of this new benzodiazepine on spontaneous coordinated motor movements were also evaluated.Male albino mice (35-40 g) from our ...

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Simultaneous determination of new thioamphetamine designer drugs in plasma by capillary electrophoresis coupled with mass spectrometry

Boatto

Nieddu

Pirisi

et al. 2007

Rapid Comm Mass Spectrometry

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A simple method for the simultaneous identification and quantification of four 2,5-methylenedioxy derivatives of 4-thioamphetamine (ALEPH series) in plasma samples was developed. The method consists of solid-phase extraction (SPE) using a Bond Elut C(18) cartridge and capillary electrophoresis coupled with electrospray ionisation mass spectrometry (CE/ESI-MS). The SPE method used required only simple steps and provided a clean extract from which identification of each drug was feasible, even at low concentrations. The method was validated according to international guidelines. The calibration curves were linear over the concentration range of 50 to 1000 ng/mL for all drugs with correlation coefficients that exceeded 0.998. The lower limits of detection of the drugs were 23-43 ng/mL. The absolute recoveries for the drugs were 64-92% and 75-96% at concentrations of 100 and 500 ng/mL, respectively. The validation data (precision, accuracy, and recovery) show the reproducibility and selectivity of the method. This clean and simple method allows the routine detection of designer drugs such as thioamphetamines which may become a serious problem in the control of illegal drugs.

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Behavioral effects of the putative anxiolytic (±)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in rats and mice

Cited by 15 publications

References 18 publications

(�)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors

(�)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors

Anxiolytic-like effects of 4-phenyl-2-trichloromethyl-3H-1,5-benzodiazepine hydrogen sulfate in mice

Simultaneous determination of new thioamphetamine designer drugs in plasma by capillary electrophoresis coupled with mass spectrometry

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