Mechanistic investigation of the stimulus properties of 1-(3-trifluoromethylphenyl) piperazine

Herndon, J. L.; Pierson, M. Edward; Glennon, Richard A.

doi:10.1016/0091-3057(92)90403-3

Cited by 40 publications

(21 citation statements)

References 30 publications

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“…For example, TFMPP and RU 24969 are now known to exhibit moderate to high affinity for 5-HT 1A/1B/1D/2A/2B and/or 2C receptors (e.g., Peroutka 1986;Schlegel and Peroutka 1986;Boess and Martin 1994;Wainscott et al 1996;Herrick-Davis et al 1998). Lastly, it has been reported that a TFMPP stimulus is not blocked by the α 1 -adrenoceptor antagonist prazosin but, curiously, is blocked by the nonselective β-adrenoceptor antagonist (−)-alprenolol (Arnt 1989;Herndon et al 1992). Nevertheless, even though the present results with 5-OMe DMT and fenfluramine might not suggest a role for 5-HT in the stimulus effect of S(−)PRO, the current findings with TFMPP and RU 24969 still hint that a role for 5-HT cannot be assumed to have been definitively eliminated as a factor in the stimulus mechanism of action of PRO.…”

Section: Discussionmentioning

confidence: 99%

S(−)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats

Young

Glennon

2008

Psychopharmacology

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Rationale Racemic propranolol (PRO), a β-adrenoceptor antagonist, has been evaluated as a test agent but not as a discriminative stimulus. Its S(−) stereoisomer is thought to subserve the effects of (±)PRO. Materials and methods Rats were trained to discriminate S(−)PRO (5 mg/kg) from saline in a two-lever foodreinforced operant conditioning task. Results The S(−)PRO stimulus was shown to be centrally mediated, dose-related, time dependent, and stereoselective: S(−)PRO (ED 50 =2.2 mg/kg) was twice as potent as (±)PRO and approximately four times as potent as R(+)PRO. The S(−)PRO stimulus generalized fully to the β-adrenoceptor agent pindolol, the α 1 -adrenoceptor agonist methoxamine, cocaine, and the serotonergic agents TFMPP and RU 24969; partial generalization occurred to (−)ephedrine and nisoxetine but not to fenfluramine or 5-OMe DMT. The S(−)PRO stimulus was blocked completely (and competitively) when prazosin, an α 1 -adrenoceptor antagonist, was given in combination with the training dose of S(−)PRO. Moreover, prazosin exerted antagonism of the S(−)PRO-like effect of (±)PRO or R(+)PRO but produced only partial antagonism of the S(−)PRO-like effect of cocaine. In a second study, rats were trained to discriminate 8 mg/kg of cocaine from saline. The cocaine stimulus generalized to S(−)PRO, (±)PRO, and R(+)PRO. Prazosin partially attenuated the stimulus effect of cocaine (8 mg/kg) but completely blocked the cocaine-like effects of (±), S(−), and R(+)PRO. Conclusions PRO and cocaine exhibited cross-substitution, but their stimulus effects were antagonized differentially by prazosin. PRO (and its optical isomers) can exert a stimulus effect that is based, at least in part, on increased α 1 -adrenoceptor activity. PRO might be better characterized as an adrenoceptor partial agonist.

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Section: Discussionmentioning

confidence: 99%

S(−)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats

Young

Glennon

2008

Psychopharmacology

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“…BZP was found to have similar pharmacological effects to amphetamine in both rats and monkeys. In contrast, TFMPP has little resemblance to dopaminergic stimulants (Fantegrossi et al 2005;Herndon et al 1992) and lacks adrenergic effects (Herndon et al 1992). In rhesus monkeys, TFMPP did not induce reinforcement of cocaine and its discriminative stimulus properties did not generalise to amphetamine (Fantegrossi et al 2005).…”

Section: Introductionmentioning

confidence: 93%

Determining the subjective effects of TFMPP in human males

et al. 2010

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Increased ratings of 'dexamphetamine-like effects', 'tension/anxiety', 'stimulated' and 'high' following TFMPP administration resemble the subjective effects of common amphetamine-type stimulants. However, increases in 'dysphoria' and 'confusion/bewilderment' ratings following TFMPP are more commonly associated with drugs that have greater effects on serotonin release, binding and reuptake such as 1-[3-chlorophenyl]-piperazine, fenfluramine and lysergic acid diethylamide.

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“…TFMPP is a nonselective serotonergic agonist, thought when used in combination with BZP to provide a mood-elevating and hallucinogen-like effect, whereas the BZP provides a "stimulatory effect" [12][13][14]. Animal studies have shown that TFMPP given alone leads to increases in 5-HT concentrations only, whereas the 1:1 combination of BZP/TFMPP at a dose of 3 mg/kg results in increases in both 5-HT and dopamine, similar to that seen with MDMA [10].…”

Section: Discussionmentioning

confidence: 99%

Dissociative and sympathomimetic toxicity associated with recreational use of 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1-benzylpiperzine (BZP)

et al. 2008

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Introduction: There is emerging evidence of increasing use of legally available synthetic compounds as recreational drugs. While there are some changes to legislation relating to these synthetic compounds, often the emergence of the agents outpaces the effect of the legislation to curb their use, and the legal status of these agents may change as more information on their toxicity becomes known. TFMPP [1-(3-trifluoromethylphenyl) piperazine] was initially temporarily controlled under Schedule I of the Controlled Substances Act in 2002 in the US, but following further review and lack of published information on toxicity, it was removed from this control in 2004. In addition, there are very few "user reports" of effects when TFMPP is taken alone or in combination with BZP [1-benzylpiperazine].Case reports: Three patients presented to our emergency department after ingesting 4 tablets thought to be 3,4-methylenedioxy-N-methylamphetamine (MDMA, street name "Ecstasy") over the course of an evening. They presented with dissociative-type symptoms, nausea, and signs consistent with sympathomimetic toxicity. All 3 improved with conservative management and observation, within 12 hours of presentation. Serum analysis demonstrated the presence of TFMPP and BZP at concentrations of 263 Ϯ 5.8 ng/mL (range 260-270 ng/mL) and 46.7 Ϯ15.3 ng/mL (range 30-60 ng/mL), respectively. No other recreational drugs were detected in an extended toxicological screen of blood and urine samples.Discussion: This is the first case series of confirmed toxicity associated with recreational use of TFMPP in combination with BZP, with clinical features not consistent with BZP toxicity. In our view, the current legal status of TFMPP should be reviewed.

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Mechanistic investigation of the stimulus properties of 1-(3-trifluoromethylphenyl) piperazine

Cited by 40 publications

References 30 publications

S(−)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats

S(−)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats

Determining the subjective effects of TFMPP in human males

Dissociative and sympathomimetic toxicity associated with recreational use of 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and 1-benzylpiperzine (BZP)

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