Propofol pretreatment induced place preference and self-administration of the tiletamine-zolazepam combination: implication on drug of abuse substitution

Peña, June Bryan de la; Ahsan, Hafiz Muhammad; Peña, Irene Joy dela; Park, Hyun Bin; Kim, Hee Jin; Sohn, Aeree; Kim, Yun Tai; Cheong, Jae Hoon

doi:10.3109/00952990.2014.920850

Cited by 3 publications

(5 citation statements)

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“…[12][13][14][15] The rewarding effects of tiletamine, zolazepam, and the tiletamine-zolazepam combination Our team has evaluated the abuse liability of the TZ combination and its constituents in the CPP and SA tests. Data from these experiments were analyzed using analysis of variance (ANOVA) followed by an appropriate post-hoc test.…”

Section: Methods Of Abuse Liability Assessment In Animalsmentioning

confidence: 99%

“…More details can be found in our previous studies. [12][13][14][15] The rewarding effects of tiletamine, zolazepam, and the tiletamine-zolazepam combination Our team has evaluated the abuse liability of the TZ combination and its constituents in the CPP and SA tests. [14] We found that the TZ combination produced neither CPP nor SA in drug-naïve rats.…”

Section: Methods Of Abuse Liability Assessment In Animalsmentioning

confidence: 99%

“…[2,8,18] Based on this assumption, we evaluated the influence of other psychoactive drugs on the rewarding effects of the TZ combination. [12,13,15] This result suggests that users or abusers of these psychoactive drugs may also potentially abuse the TZ combination. [43] These drugs may be used therapeutically and recreationally.…”

Section: Effects Of Other Psychoactive Drugs On the Rewarding Effectsmentioning

confidence: 98%

“…[45] We have found that preexposure to ketamine, diazepam, propofol, and ethanol, but not to caffeine or nicotine, induced CPP and/or SA towards the TZ combination (Table 3). [12,13,15] This result suggests that users or abusers of these psychoactive drugs may also potentially abuse the TZ combination.…”

Section: Effects Of Other Psychoactive Drugs On the Rewarding Effectsmentioning

confidence: 98%

“…Cases of human abuse of the TZ combination, found from our review of the literature, are presented and discussed. Moreover, findings from our preclinical studies, [12][13][14][15] where the rewarding effects of the TZ combination and its constituents were evaluated, are also compiled and reviewed. Ultimately, this paper seeks to help in increasing the awareness of law enforcement, regulatory agencies, and healthcare workers of the dangers of this psychoactive drug and its related substances.…”

Section: Introductionmentioning

confidence: 99%

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The abuse liability of the NMDA receptor antagonist‐benzodiazepine (tiletamine‐zolazepam) combination: evidence from clinical case reports and preclinical studies

Peña

Cheong

2016

Drug Testing and Analysis

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The tiletamine-zolazepam (TZ) combination is an anaesthetic drug commonly used in veterinary medicine. It is an equal amount combination of tiletamine, a dissociative anaesthetic pharmacologically classified as an N-methyl-D-aspartate (NMDA) receptor antagonist, and zolazepam, a benzodiazepine tranquilizer. There are concerns regarding the safety profile of this drug combination due to incidents of human misuse/abuse. In this paper, we discuss the abuse liability of this drug combination based on currently available scientific evidence. We performed an in-depth search of medical and scientific literature and found seven reported cases of human abuse of the TZ combination, two of which resulted in fatal outcomes. In most of these cases, drug administration was intentional indicating that the TZ combination was abused by humans. This finding is bolstered by the results of preclinical studies showing that the TZ combination produces rewarding effects in rats, although manifested only in pretreated subjects. Further studies revealed that the addictive effects of the TZ combination are influenced by pre-exposure to other psychoactive drugs. Pre-exposure to ketamine, diazepam, propofol, or ethanol facilitated the expression of the rewarding effects of the TZ combination. These findings support the hypothesis that the TZ combination was and can be used as a substitute or replacement drug. Altogether, the compiled evidence indicates that the TZ combination can potentially be abused by humans. Thus, careful use, dispensation, and monitoring of the TZ combination and associated substances are strongly advocated. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Methods Of Abuse Liability Assessment In Animalsmentioning

confidence: 99%

Section: Methods Of Abuse Liability Assessment In Animalsmentioning

confidence: 99%

Section: Effects Of Other Psychoactive Drugs On the Rewarding Effectsmentioning

confidence: 98%

Section: Effects Of Other Psychoactive Drugs On the Rewarding Effectsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The abuse liability of the NMDA receptor antagonist‐benzodiazepine (tiletamine‐zolazepam) combination: evidence from clinical case reports and preclinical studies

Peña

Cheong

2016

Drug Testing and Analysis

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Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential

Botanas

Peña

et al. 2015

Pharmacology Biochemistry and Behavior

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Regulatory Effects of Propofol on High-Dose Remifentanil-Induced Hyperalgesia

Su¹,

Zhu

Tian³

et al. 2020

Physiol Res

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We aimed to evaluate the regulatory effects of propofol on high-dose remifentanil-induced hyperalgesia. A total of 180 patients receiving laparoscopic cholecystectomy were randomly divided into sevoflurane + high-dose remifentanil (SH) group, sevoflurane + low-dose remifentanil (SL) group and propofol + high-dose remifentanil group (PH) group (n=60). After intravenous administration of midazolam, SH and SL groups were induced with sevoflurane and remifentanil, and PH group was induced with propofol and remifentanil. During anesthesia maintenance, SH and SL groups were given 0.3 μg/kg/min and 0.1 μg/kg/min sevoflurane and remifentanil respectively, and PH group was given 0.3 μg/kg/min propofol and remifentanil. The three groups had significantly different awakening time, extubation time and total dose of remifentanil (P<0.001). Compared with SL group, periumbilical mechanical pain thresholds 6 h and 24 h after surgery significantly decreased in SH group (P<0.05), and the visual analog scale (VAS) scores significantly increased 30 min, 2 h and 6 h after surgery (P<0.05). Compared with SH group, periumbilical mechanical thresholds 6 h and 24 h after surgery were significantly higher in PH group (P<0.05), and VAS scores 30 min, 2 h and 6 h after surgery were significantly lower (P<0.05). PH group first used patient-controlled intravenous analgesia pump significantly later than SL group did (P<0.05). The total consumptions of sufentanil in PH and SL groups were significantly lower than that of SH group (P<0.05). The incidence rates of bradycardia and postoperative chill in PH and SH groups were significantly higher than those of SL group (P<0.05). Anesthesia by infusion of high-dose remifentanil plus sevoflurane caused postoperative hyperalgesia which was relieved through intravenous anesthesia with propofol.

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Propofol pretreatment induced place preference and self-administration of the tiletamine-zolazepam combination: implication on drug of abuse substitution

Abstract: These results suggest that tiletamine-zolazepam combinations might be used as a "substitute drug" by abusers of propofol. The careful use, dispensation, and monitoring of tiletamine-zolazepam combinations are advocated.

Cited by 3 publications

References 19 publications

The abuse liability of the NMDA receptor antagonist‐benzodiazepine (tiletamine‐zolazepam) combination: evidence from clinical case reports and preclinical studies

The abuse liability of the NMDA receptor antagonist‐benzodiazepine (tiletamine‐zolazepam) combination: evidence from clinical case reports and preclinical studies

Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential

Regulatory Effects of Propofol on High-Dose Remifentanil-Induced Hyperalgesia

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