Disease relevance of dextroamphetamine

• Although it induces stereotype activity by increased DA activity, L-amphetamine, like fenfluramine and p-chloroamphetamine, inhibits the lordosis response by some other action presumably related to serotonergic mechanisms [1].
• The effects of various 5-HT receptor subtype-selective antagonists were studied on phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia in Wistar rats, in an attempt to characterize the 5-HT receptor subtype mediating DOI-induced hyperthermia [2].
• CONCLUSIONS: Pretreatment weight, adjusted for age, gender, and height, is a significant predictor of weight loss in children with ADHD treated with either MPH or DEX [3].
• In Fischer rats, AMPT-induced locomotion was increased by C-section under maternal anesthesia but decreased by C-section after maternal decapitation, compared with vaginal birth [4].
• Compared to control animals, MD rats showed (1) a reduction in body weight, (2) an increased in reversal latency in negative geotaxis, (3) a delayed eye opening, (4) a delayed emergence of walking and rearing; and (5) a delayed emergence of the behavioural response to amphetamine (amph) [5].

Psychiatry related information on dextroamphetamine

• Two experiments examined the effects of various doses of l-amphetamine on locomotor activity, two-way avoidance, and intertrial responses in rats that were 15, 17, 21, 36, and 90 days of age [6].
• Sleep deprivation deficits and their reversal by d- and l-amphetamine [7].
• Acute administration of d-amphetamine (up to 8 mg/kg) or l-amphetamine (up to 12 mg/kg) in the marmoset results in a dose-dependent increase in small head movements (checking), an almost total suppression of activities including eating, grooming, playing, and social interaction, but little change in the amount of movement [8].
• In an attempt to examine the possible role of noradrenergic (NA) and dopaminergic (DA) systems in intracranial self-stimulation (ICS), the rate-increasing effects of D- and L-amphetamine on ICS were determined in rats with nucleus accumbens electrodes (DA placement) or dorsal NA bundle electrodes (NA placement) [9].
• Under these conditions, AMPH nearly doubled appetitive behavior at doses that decreased food intake by nearly 50 percent [10].

High impact information on dextroamphetamine

• The (+/-)phenylisopropylamine analogues had significantly higher intrinsic activities for 5-HT 2A receptor-mediated hydrolysis of phosphatidyl inositol compared to their phenethylamine analogues [11].
• In aODN-pretreated rats a strong reduction of the AMPH, but not of the COC-stimulated DA efflux from nucleus accumbens was observed [12].
• The inversion of vesicular transporters and/or intravesicular alkalinization is assumed to have a role in AMPH-induced exocytosis [12].
• We investigated the possible involvement of a Shaker-like Kv1.1 channel subtype in the central effects of AMPH, using an antisense oligodeoxyribonucleotide (aODN) that specifically and reversibly inhibits the expression of these channels in the brain [12].
• We tested this hypothesis in human embryonic kidney 293 cells stably transfected with the human DAT by measuring the uptake of dopamine, tyramine, and D- and L-amphetamine as well as substrate-induced release of preloaded N-methyl-4-[3H]phenylpyridinium ([3H]MPP+) [13].

Chemical compound and disease context of dextroamphetamine

• Amphetamine (AMPH), which increases dopamine, decreased food intake at doses that did not affect appetitive behavior, indicating that appetitive and consummatory aspects of eating can be pharmacologically differentiated [10].
• Investigation of the role of noradrenaline (NA) and dopamine (DA) in self-stimulation showed that d-amphetamine (which releases more DA than does l-amphetamine, but not more NA) was much more effective than l-amphetamine in enhancing self-stimulation of NA sites in the locus coeruleus and near-lateral hypothalamus [14].
• In contrast to AMPH, THC produced no direct effect on MEPH-induced gnawing but caused a strong suppression of MEPH-induced locomotor activity [15].
• In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC) [16].
• Rats administered chronic haloperidol (5 mg/cc) for 2 months exhibited stereotyped gnawing during chronic haloperidol treatment, and after withdrawal from haloperidol, showed significantly greater stereotyped behavior induced by apomorphine or L-amphetamine compared to saline controls [17].

Biological context of dextroamphetamine

• A comparison of the kinetics of d- and l-amphetamine in the brain of isolated and aggregated rats [18].
• Blood pressure and heart rate responses evoked by d- and l-amphetamine in the pithed rat preparation [19].
• Effects of d- and l-amphetamine on food intake: evidence for a dopaminergic substrate [20].
• Since diuresis is selectively enhanced by kappa agonists, its sensitivity to chronic AMPH was also evaluated [21].
• While AMPH restricted the range in both genotypes, characterizing the geographical region in which the restriction took place further differentiated the genotypes [22].

Anatomical context of dextroamphetamine

• The results suggest that the hormonal responses to both D- and L-amphetamine were mediated by noradrenergic neurones stimulatory to GH and inhibitory to ACTH, and that D- and L-amphetamine exert equipotent noradrenergic effects in the neuroendocrine system [23].
• Increased sensitivity to d- and l-amphetamine action after midbrain raphe lesions as measured by locomotor activity [24].
• Release of 3H-doapamine or of 3H-norepinephrine and inhibition of accumulation of 3H-dopamine or 3H-norepinephrine by d- and l-amphetamine were studied in slices of rat neostriatum and in slices of rat cerebral cortex [25].
• When L: -amphetamine was locally applied, DA release was not significantly different in amplitude, and it exhibited the same rapid kinetics of D: ,L: -amphetamine.CONCLUSIONS: These data support the hypothesis that amphetamine isomers have different effects on release of DA from nerve endings [26].
• This study provides a detailed comparison of their effects on the synaptosomal and vesicular accumulation of dopamine (DA) and noradrenaline (NA) and release in vitro in rat prefrontal cortex and striatum. d-Amphetamine was more potent than l-amphetamine at inhibiting accumulation of DA or NA in synaptosomes and vesicles [27].

Associations of dextroamphetamine with other chemical compounds

• Experiments compared a series of phenethylamine hallucinogens with their phenylisopropylamine analogues for binding affinity and ability to stimulate serotonin 5-HT 2A receptor-mediated hydrolysis of phosphatidyl inositol in cells expressing cloned rat and human 5-HT 2A receptors [11].
• The two stereoisomers of amphetamine were equally potent as inhibitors of accumulation in the cortex, whereas d-amphetamine was approximately 3-fold more potent than l-amphetamine in the neostriatum [25].
• Using linear regression analysis, significant correlations were found between pretreatment weight and change in weight for both the MPH-treated group (r = .63) and the DEX-treated group (r = .47) [3].
• Release of endogenous dopamine by d- or l-amphetamine (10 and 50 mug) in the nucleus accumbens produced a rise in coordinated activity, the d-isomer was about 4 times as potent as the l-isomer, and the effect of the d-isomer was blocked completely by alpha-methyltyrosine [28].
• The phenylisopropylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats [29].

Gene context of dextroamphetamine

• Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors [30].
• Evidence from studies with phenylisopropylamine hallucinogens indicates that the 5HT2A receptor is the likely target for the initiation of events leading to hallucinogenic activity associated with LSD and related drugs [31].
• Changes in mRNA levels for heat-shock/stress proteins (Hsp) and a secretory vesicle associated cysteine-string protein (Csp1) after amphetamine (AMPH) exposure [32].
• MAO-A did not differ among the saline, amphetamine, and young control rats, but MAO-B was significantly higher in the middle aged saline and L-amphetamine rats than in the young controls [33].
• Effect of d- and l-amphetamine on rat plasma prolactin levels [34].

Analytical, diagnostic and therapeutic context of dextroamphetamine

• In addition, changes in electroencephalograms and behavior of rats induced by l-deprenyl and l-amphetamine were different from those produced by the d-enantiomers [35].
• Intravenous self-administration of d- and l-amphetamine by dog [36].
• N-(Trifluoroacetyl)-l-prolyl- (N-TFA-l-prolyl-) d- and l-amphetamine diastereoisomers were separated by high-performance liquid chromatography and confirmed by an interfaced mass spectrometer system, using the commercially available N-3,5-(dinitrobenzoyl)phenylglycine chiral column [37].
• The authors observed significant cross-reactivity of L-amphetamine with the amphetamine immunoassay also marketed by Abbott Laboratories and run on the AxSYM analyzer [38].
• Animals that eat and/or drink in response to electrical stimulation of the lateral hypothalamus (ESLH-pos) are more responsive to both schedule-induced polydipsia (SIP) tests and a series of amphetamine (AMPH) injections than animals that do not exhibit these behaviors (ESLH-neg) [39].

References