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

Fantegrossi, William E.; Reissig, Chad J.; Katz, Elyse; Yarosh, Haley L.; Rice, Kenner C.; Winter, J.C.

doi:10.1016/j.pbb.2007.09.007

Cited by 64 publications

(58 citation statements)

References 40 publications

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“…As one illustration, Fantegrossi et al (2008b) examined the effects of N,N-dipropyltryptamine (DPT) in the mouse HTR and in rat drug discrimination assays. Rats were trained to discriminate LSD, psilocybin, or MDMA from saline; in addition, one group of rats was trained to discriminate DPT from saline.…”

Section: F Possible Role Of Other Receptorsmentioning

confidence: 99%

“…By contrast, 0.1 mg/kg M100907 completely blocked the MDMA-like stimulus properties of DPT. Fantegrossi et al (2008b) also trained rats to discriminate 1.5 mg/kg DPT from saline. The discriminative stimulus effects of DPT were not affected by prior treatment with WAY-100635, but they were significantly attenuated by pretreatment with 0.1 mg/kg M100907.…”

Section: F Possible Role Of Other Receptorsmentioning

confidence: 99%

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Psychedelics

Nichols

2016

Pharmacological Reviews

1,271

1,265

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Section: F Possible Role Of Other Receptorsmentioning

confidence: 99%

Section: F Possible Role Of Other Receptorsmentioning

confidence: 99%

Psychedelics

Nichols

2016

Pharmacological Reviews

1,271

1,265

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“…That seems to be the case both for agonists and for antagonists. DOM and 2C-T-7 have similar potency, and both are 3-fold more potent than DPT in producing head twitching in mice (Fantegrossi et al, 2005(Fantegrossi et al, , 2008b, an effect that is thought to be mediated by 5-HT 2A receptors. Based on apparent pA 2 values, ketanserin and ritanserin have very similar potency in antagonizing the discriminative stimulus effects of each agonist, being 10-to 17-fold less potent than MDL100907 Fig.…”

Section: Discussionmentioning

confidence: 99%

“…2C-T-7 is a "designer" phenethylamine with hallucinogenic activity and high affinity at 5-HT 2A and 5-HT 2C receptors; however, the behavioral effects of 2C-T-7, including discriminative stimulus effects in nonhuman primates (Li et al, 2008), seem to be mediated by 5-HT 2A receptors (Fantegrossi et al, 2005). DPT, a tryptamine with hallucinogenic activity, recently was shown to have agonist activity at 5-HT 2A and 5-HT 1A receptors (Li et al, 2007;Fantegrossi et al, 2008b). …”

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confidence: 99%

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-Methylphenyl)-2-Aminopropane in Rhesus Monkeys: Antagonism and Apparent p A2 Analyses

Rice

2009

The Journal of Pharmacology and Experimental Therapeutics

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Discriminative stimulus effects of the serotonin (5-HT) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) have been studied in rats and, more recently, in rhesus monkeys. This study examined DOM, 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), and dipropyltryptamine hydrochloride (DPT) alone and in combination with three antagonists, MDL100907 , to identify the 5-HT receptor subtype(s) that mediates the discriminative stimulus effects of these 5-HT receptor agonists. Four adult rhesus monkeys discriminated between 0.32 mg/kg s.c. DOM and vehicle while responding under a fixed ratio 5 schedule of stimulus shock termination. DOM, 2C-T-7, and DPT dose-dependently increased responding on the DOM-associated lever. MDL100907 (0.001-0.01 mg/kg), ketanserin (0.01-0.1 mg/kg), and ritanserin (0.01-0.1 mg/kg) each shifted the dose-response curves of DOM, 2C-T-7, and DPT rightward in a parallel manner. Schild analysis of each drug combination was consistent with a simple, competitive, and reversible interaction. Similar apparent affinity (pA 2 ) values were obtained for MDL100907 in combination with DOM (8.61), 2C-T-7 (8.58), or DPT (8.50), for ketanserin with DOM (7.67), 2C-T-7 (7.75), or DPT (7.71), and for ritanserin with DOM (7.65), 2C-T-7 (7.75), or DPT (7.65). Potency of antagonists in this study was correlated with binding affinity at 5-HT 2A receptors and not at 5-HT 2C or ␣ 1 adrenergic receptors. This study used Schild analysis to examine receptor mechanisms mediating the discriminative stimulus effects of hallucinogenic drugs acting at 5-HT receptors; results provide quantitative evidence for the predominant, if not exclusive, role of 5-HT 2A receptors in the discriminative stimulus effects of DOM, 2C-T-7, and DPT in rhesus monkeys.Phenethylamines and tryptamines are two classes of drugs that act at serotonin (5-HT) receptors and can produce hallucinations; in general, agonists from these two classes have similar but not identical behavioral and neurochemical effects. For example, many phenethylamines bind relatively nonselectively to 5-HT 2A and 5-HT 2C receptors and have comparatively lower (e.g., 1000-fold) affinity for other (e.g., 5-HT 1A ) 5-HT receptors. Tryptamines, on the other hand, often display higher affinity than phenethylamines for 5-HT 1A receptors (for review, see Nichols, 2004;Fantegrossi et al., 2008a) and comparatively lower affinity for 5-HT 2A and 5-HT 2C receptors. Despite differences between phenethylamines and tryptamines in their binding selectivity for different 5-HT receptors, with few exceptions (e.g., Winter et al., 2000), agonists from these chemical classes have similar effects that seem to be mediated predominantly by 5-HT 2A receptors (e.g., Vollenweider et al., 1998).Drug discrimination is used to study receptor mechanisms that mediate the effects of drugs from a variety of pharmacologic classes. Many drugs with hallucinogenic effects in humans have agonist actions at 5-HT receptors, and among those drugs, the discriminative stimulus effects o...

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“…In a particularly interesting study, Blair et al (2000) reported that ring fluorination of hallucinogenic tryptamines reduced the degree of mimicry of the stimulus effects of LSD by these drugs while at the same time diminishing their affinity for the 5-HT 1A receptor. The tryptamines, ranging from classic agents such as DMT (Sai-Halasz et al 1958) to a series of ring-and amine-substituted agents such as DPT (Fantegrossi et al 2008b;Li et al 2008), 2,5-dimethoxy-4-n-propylthiophenethylamine (Fantegrossi et al 2005), and 5-methoxy-N,N-diisopropyltryptamine (Fantegrossi et al 2006), are unquestionably hallucinogenic (Shulgin and Shulgin 1997) yet binding data regularly indicate that their highest affinity is for 5-HT 1A receptors. Indeed, a study by Spencer et al (1987) concluded that stimulus control by 5-MeO-DMT in the rat is mediated by 5-HT 1A receptors.…”

Section: Neurochemical Bases Of Stimulus Control By Hallucinogensmentioning

confidence: 99%

Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines

Winter

2008

Psychopharmacology

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Background Although man's first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species. Objective The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine.Results The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT 2A receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT 2C and 5-HT 1A receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities. Conclusions Hallucinogen-induced stimulus control provides a unique behavioral tool for the prediction of subjective effects in man and for the elucidation of the pharmacological mechanisms of the action of these agents.

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

Cited by 64 publications

References 40 publications

Psychedelics

Psychedelics

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-Methylphenyl)-2-Aminopropane in Rhesus Monkeys: Antagonism and Apparent p A2 Analyses

Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines

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