Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice

Fantegrossi, William E.; Kiessel, Christina Lynn; Leach, Prescott T.; Martin, Cathy; Karabenick, Rachel Lynn; Chen, X.; Ohizumi, Yasushi; Ullrich, Thomas; Rice, Kenner C.; Woods, James H.

doi:10.1007/s00213-003-1741-2

Cited by 46 publications

(52 citation statements)

References 28 publications

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“…These antagonist doses were chosen based upon our previous demonstrations of their effectiveness against the behavioral effects of other tryptamines (e.g., Fantegrossi et al, 2006). Methods for measuring drug-elicited head twitch behavior have been previously described (Corne et al, 1963;Corne and Pickering, 1969;Boulton and Handley, 1973;Fozard and Palfreyman, 1979;Green et al, 1983;Fantegrossi et al, 2004). For the present experiments, ten minutes after the initial injection, mice were injected with various doses of DPT or saline, then returned to the small observation cage.…”

Section: Methodsmentioning

confidence: 99%

“…The drug-elicited head twitch response (HTR) (Corne et al, 1963;Corne and Pickering, 1969) is considered to be a selective behavioral model for 5-HT 2 agonist activity in the rodent, and several previous studies have established that direct and indirect 5-HT agonists induce this effect (Peroutka et al, 1981;Colpaert and Janssen, 1983;Green et al, 1983;Goodwin and Green, 1985;Darmani et al, 1990a;1990b;1992;Fantegrossi et al, 2004;. Further, 5-HT 2 receptor antagonists selectively block head twitch behavior (Lucki et al, 1984;Handley and Singh, 1986;Fantegrossi et al, 2004;, and their potency in this regard is highly correlated with the antagonist's affinity for 5-HT 2 receptors (Peroutka et al, 1981;Ortmann et al, 1982).…”

mentioning

confidence: 99%

“…Further, 5-HT 2 receptor antagonists selectively block head twitch behavior (Lucki et al, 1984;Handley and Singh, 1986;Fantegrossi et al, 2004;, and their potency in this regard is highly correlated with the antagonist's affinity for 5-HT 2 receptors (Peroutka et al, 1981;Ortmann et al, 1982). Importantly, HTR is not elicited by non-hallucinogenic 5-HT 2A agonists such as lisuride and quipazine in the mouse (Gonzalez-Maeso et al, 2003;Gonzalez-Maeso et al, 2007), although reports of quipazine-induced HTR in the rat are abundant (e.g., Seeger et al, 1995;Eison and Yocca, 1985;Yocca et al, 1990).…”

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confidence: 99%

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Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): Possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents

Fantegrossi¹,

Reissig

Katz³

et al. 2008

Pharmacology Biochemistry and Behavior

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N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptamine (psilocybin), or 3,4-methylenedioxymethamphetamine (MDMA). A separate group of rats was also trained to recognize DPT itself as a discriminative stimulus, and in all cases, the behavioral effects of DPT were challenged with the selective serotonin (5-HT) 2A antagonist M100907, the 5-HT 1A selective antagonist WAY-100635, or their combination. In the head twitch assay, DPT elicited dosedependent effects, producing a biphasic dose-effect curve. WAY-100635 produced a parallel rightward shift in the dose-effect curve for head twitches, indicative of surmountable antagonism, but the antagonist effects of M100907 were functionally insurmountable. DPT produced partial to full substitution when tested in rats trained to discriminate LSD, psilocybin or MDMA, and served as a discriminative stimulus. In all cases, the antagonist effects of M100907 were more profound than were those of WAY-100635. DPT is thus active in two rodent models relevant to 5-HT 2 agonist activity. The effectiveness with which M100907 antagonizes the behavioral actions of this compound strongly suggests that the 5-HT 2A receptor is an important site of action for DPT, but the modulatory actions of WAY-100635 also imply a 5-HT 1A -mediated component to the actions of this compound.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): Possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents

Fantegrossi¹,

Reissig

Katz³

et al. 2008

Pharmacology Biochemistry and Behavior

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“…Cole and Sumnall 2003;Green et al 2003;Simantov 2004). Recently, however, Sprague et al (2003) have shown that α 1 adrenoceptors are involved in the hyperthermic response to MDMA, and Fantegrossi et al (2004) reported that the α 1 -adrenoceptor antagonist prazosin blocked the hyperthermia and locomotor increase induced by MDMA in mice. No microdialysis data have been reported to indicate whether MDMA enhances central extracellular NE concentrations.…”

Section: Introductionmentioning

confidence: 99%

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

Selken

Nichols

2007

Pharmacology Biochemistry and Behavior

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The recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) increases locomotor activity when administered to rats. Although the published pharmacology of MDMA has focused almost exclusively on the roles of serotonin and dopamine, in vitro studies indicate that MDMA induces serotonin and norepinephrine release with equal potency. The present experiments tested the hypothesis that blockade of α 1 -adrenoceptors with systemic or local administration of the antagonist prazosin would attenuate the locomotor response to systemic administration of (±)-MDMA. Pretreatment with systemic prazosin (0.5 mg/kg) or microinjections into either the prefrontal cortex or ventral tegmental area completely blocked the locomotor stimulant effects of 5 mg/kg (±)-MDMA, assessed using a computerized Behavioral Pattern Monitor. Prazosin was more potent in blocking the locomotor stimulant effects of (±)-MDMA than a 2 mg/kg dose of (+)-amphetamine that produced a similar locomotor activity increase. These results indicate that activation of α 1 -adrenoceptors in both the prefrontal cortex and ventral tegmental areas modulate the locomotor response to MDMA.

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“…The alkaloid nantenine (9,10-methylenedioxy-1,2-dimethoxyaporphine) is a naturally-occurring compound from the fruit of Nandina domestica that bears structural similarity to MDMA. Nantenine is reported to antagonize many of the effects of MDMA in mice [87]. Because MDMA is a substrate of the monoamine transporters, nantenine could block the effects of MDMA by acting as a monoamine reuptake inhibitor.…”

Section: Miscellaneous Drugsmentioning

confidence: 99%

Therapeutic Potential of Monoamine Transporter Substrates

Rothman¹,

Baumann²

2006

CTMC

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Monoamine transporter proteins are targets for many psychoactive compounds, including therapeutic and abused stimulant drugs. This paper reviews recent work from our laboratory investigating the interaction of stimulants with transporters in brain tissue. We illustrate how determining the precise mechanism of stimulant drug action (uptake inhibitor vs. substrate) can provide unique opportunities for medication discovery. An important lesson learned from this work is that drugs which display equipotent substrate activity at dopamine (DA) and serotonin (5-HT) transporters have minimal abuse liability and few stimulant side-effects, yet are able to suppress ongoing drug-seeking behavior. As a specific example, we describe the development of PAL-287 (α-methylnapthylethylamine), a dual DA/5-HT releasing agent that suppresses cocaine self-administration in rhesus monkeys, without the adverse effects associated with older phenylethylamine 5-HT releasers (e.g., fenfluramine) and DA releasers (e.g., amphetamine). Our findings demonstrate the feasibility of developing non-amphetamine releasing agents as potential treatments for substance abuse disorders and other psychiatric conditions.

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Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice

Abstract: Nantenine functions as an effective antagonist against a wide range of MDMA-induced effects in mice. The antagonist actions of this compound at serotonin and adrenergic receptors may be differentially implicated across endpoints.

Cited by 46 publications

References 28 publications

Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): Possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents

Hallucinogen-like effects of N,N-dipropyltryptamine (DPT): Possible mediation by serotonin 5-HT1A and 5-HT2A receptors in rodents

α1-Adrenergic receptors mediate the locomotor response to systemic administration of (±)-3,4-methylenedioxymethamphetamine (MDMA) in rats

Therapeutic Potential of Monoamine Transporter Substrates

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