(–)Ephedrine and Caffeine Mutually Potentiate One Another’s Amphetamine-Like Stimulus Effects

Young, Richard; Gabryszuk, M.; Glennon, Richard A.

doi:10.1016/s0091-3057(98)00044-6

Cited by 42 publications

(29 citation statements)

References 11 publications

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“…For example, the ED 50 for nicotine (0.054 mg/kg) was in the lower end of the range described for operant conditioning experiments using a 0.4 mg/kg training dose (0.05 mg/kg (Gasior et al, 1999), 0.087 mg/kg (Chance et al, 1977), and 0.14 mg/kg (Pratt et al, 1983)). The ED 50 for amphetamine (0.281 mg/kg) was also within the range described in operant drug discrimination experiments employing a 1 mg/kg training dose (0.26 mg/kg and 0.40 mg/kg (Young et al, 1998)]. Also similar to previous findings using operant drug discrimination procedures, CDP did not substitute for any of the stimulants that we trained as drug features (eg Stolerman et al, 1984), nor did any stimulant substitute for CDP (eg Gauvin et al, 1994).…”

Section: Discussionsupporting

confidence: 64%

“…In humans, caffeine (300 mg) partially substitutes (60% drug-appropriate responding) for the stimulus effects of amphetamine (10 mg; Chait and Johanson, 1988). In rats, some researchers have found that caffeine fully substitutes for 1 mg/kg amphetamine (Young et al, 1998), whereas others found only partial substitution (Clark et al, 1995). Notably, we found caffeine substitution at much lower doses than that reported by Young and colleagues (1998) despite using an identical amphetamine training dose (1 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Palmatier

Wilkinson

Metschke

et al. 2004

Neuropsychopharmacol

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Recent experiments from our laboratory have demonstrated that drug states can signal when environmental cues will be followed by rewarding outcomes (ie Pavlovian conditioning). However, little is known about the generality of this approach and whether it can be used for studying the pharmacological properties of drug states. Accordingly, the present experiments tested the pharmacological specificity of nicotine (0.4 mg/kg), amphetamine (1 mg/kg), and chlordiazepoxide (CDP, 5 mg/kg) in this Pavlovian drug discrimination procedure. Following drug administration, presentation of a conditional stimulus (CS) was followed by brief access to sucrose. When saline was administered, the same CS was presented but sucrose was withheld. In substitution tests, rats in each condition received varying doses of all training drugs and caffeine. Anticipatory food seeking developed during the CS on drug sessions but not on saline sessions for all drug features (ie drug state-specific conditional response (CR)). In generalization tests, this CR decreased as a function of decreases in the training dose. Median effective doses (ED 50 s) were calculated for nicotine (0.054 mg/kg), amphetamine (0.26 mg/kg), and CDP (2.48 mg/kg). No compound tested substituted for the CDP training drug. Partial substitution was evident between nicotine and amphetamine; CDP did not substitute for either of these drug features. Caffeine fully substituted for nicotine (ED 50 ¼ 15.45 mg/kg) and amphetamine (ED 50 ¼ 3.70 mg/kg), but not for CDP. These results are consistent with the hypothesis that drug states can occasion appetitive Pavlovian CRs in a pharmacologically specific manner.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Palmatier

Wilkinson

Metschke

et al. 2004

Neuropsychopharmacol

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“…Using rats trained to discriminate 1 mg/kg of (+)-amphetamine from a saline vehicle in a two-lever drug discrimination test procedure, it was shown that (-)-ephedrine, but not (+)-ephedrine, substitutes for the (+)-amphetamine stimulus (Young et al, 1998).…”

Section: Ephedrinementioning

confidence: 99%

“…Doses of (-)-ephedrine and caffeine, which produced < 1 % drug-appropriate response when administered alone, were able to enhance the stimulus effects of the other, when administered in combination. According to the authors low doses of (-)-ephedrine and caffeine may mutually potentiate one another's stimulus effects in (+)-amphetamine-trained rats (Young et al, 1998).…”

Section: Dogsmentioning

confidence: 99%

Untitled

2013

EFSA Journal

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The ANS Panel provides a scientific opinion evaluating the safety in use of Ephedra herb and its preparations originating from Ephedra species when used in food, e.g. in food supplements. Ephedra species contain alkaloids of biological relevance: ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine (cathine), methylephedrine and methylpseudoephedrine. They have sympathomimetic activity and some of them are also used as active ingredients in medicinal products for which adverse effects are described. The use of Ephedra herb in food supplements is prohibited in several European countries, however food supplements containing Ephedra herb, also in combination with caffeine, are offered for sale via the internet. The Panel reviewed the available scientific data on a possible association between the intake of Ephedra herb, its preparations or its alkaloids and potential harmful effects on health. There is wide variation in the concentration of the individual ephedra alkaloids in different Ephedra species and in their preparations for use in food. No adequately specified individual preparations of Ephedra herb are known for which sufficient toxicological data for hazard characterisation exist. Due to the absence of adequate data on genotoxicity, short-term, long-term and reproductive and developmental toxicity the Panel could not provide advice on a daily intake of Ephedra herb and its preparations that do not give rise to concerns about harmful effects to health. Ephedra herb and its preparations in food supplements may result in exposure to total ephedra alkaloids or ephedrine which falls within or may exceed the therapeutic dose ranges for the individual ephedra alkaloids or ephedrine, respectively, in medicinal products. Such an exposure could lead to severe adverse effects, which may be enhanced by the combination with caffeine. The Panel concluded that Ephedra herb and its preparations containing ephedra alkaloids used as food supplements were of significant safety concern at the estimated use levels. In particular, EFSA was requested to review the existing scientific data on the possible link between the intake of Ephedra species and harmful effects on health, and to provide advice on a tolerable upper intake level (UL) for Ephedra species for the general population, and as appropriate, for vulnerable subgroups of the population. In the absence of a tolerable upper intake level, EFSA was asked to provide advice on a daily intake of Ephedra species that does not give rise to concerns about harmful effects to health.The risk assessment was performed by the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS Panel) in accordance with the 2009 EFSA Guidance on safety assessment of botanicals and botanical preparations intended for use as ingredients in food supplements.In addressing the Terms of Reference of this request, the ANS Panel noted that the term -tolerable upper intake level‖, was used by EFSA so far only for nutrients, such as vitamins or minerals, to describe the maximum ...

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“…The ephedra has historically been used by Asian cultures for its effectiveness as an anti-asthmatic and central nervous system (CNS) stimulant, as well as for its ability to induce an intoxicated state. 2 Ephedrine was initially isolated and identified as the primary active alkaloid responsible for the effects of ephedra by Chen and Schmidt in 1924. Ephedrine causes an increase in systemic arterial pressure, heart rate, and cardiac output.…”

Section: Introductionmentioning

confidence: 99%