Designer Drugs

2022 ◽  
pp. 185-194
Author(s):  
Neelambika Revadigar ◽  
Ching Tary Yu ◽  
Isabelle Silverstone-Simard
Keyword(s):  
Designer Drugs

1769-P: Microglial Activation and Inactivation via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) Alters Peripheral Glucose Homeostasis

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1769-P
Author(s):  
KELLY M. NESS ◽  
JOHN DOUGLASS ◽  
MARTIN VALDEARCOS-CONTRERAS ◽  
MAURICIO D. DORFMAN ◽  
ANZELA NIRAULA ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Microglial Activation ◽  
Designer Drugs

Designer drugs: popular among teenagers

Pediatru ro ◽  
2017 ◽  
Vol 2 (46) ◽  
Author(s):  
Violeta Ștreangă ◽  
Mirela Popa ◽  
Cristina Jităreanu ◽  
Aniela Rugină ◽  
Nicolai Nistor ◽  
...  
Keyword(s):  
Designer Drugs

scholarly journals A38 TRPV1 VISCERAL AFFERENTS CONTROL CENTRAL SENSITIZATION IN IBD

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 278-279
Author(s):  
M Defaye ◽  
N Abdullah ◽  
M Iftinca ◽  
C Altier
Keyword(s):  
Chronic Pain ◽  
Central Sensitization ◽  
Microglial Activation ◽  
Visceral Pain ◽  
Purinergic Signaling ◽  
Designer Drugs ◽  
Visceral Afferents ◽  
Peripheral Sensitization ◽  
Specific Expression

Abstract Background Long-lasting changes in neural pain circuits precipitate the transition from acute to chronic pain in patients living with inflammatory bowel diseases (IBDs). While significant improvement in IBD therapy has been made to reduce inflammation, a large subset of patients continues to suffer throughout quiescent phases of the disease, suggesting a high level of plasticity in nociceptive circuits during acute phases. The establishment of chronic visceral pain results from neuroplasticity in nociceptors first, then along the entire neural axis, wherein microglia, the resident immune cells of the central nervous system, are critically involved. Our lab has shown that spinal microglia were key in controlling chronic pain state in IBD. Using the Dextran Sodium Sulfate (DSS) model of colitis, we found that microglial G-CSF was able to sensitize colonic nociceptors that express the pain receptor TRPV1. While TRPV1+ nociceptors have been implicated in peripheral sensitization, their contribution to central sensitization via microglia remains unknown. Aims To investigate the role of TRPV1+ visceral afferents in microglial activation and chronic visceral pain. Methods We generated DREADD (Designer Receptors Exclusively Activated by Designer Drugs) mice in which TRPV1 sensory neurons can be inhibited (TRPV1-hM4Di) or activated (TRPV1-hM3Dq) in a time and tissue specific manner using the inert ligand Clozapine-N-Oxide (CNO). To test the inhibition of TRPV1 neurons in DSS-induced colitis, TRPV1-hM4Di mice were treated with DSS 2.5% or water for 7 days and received vehicle or CNO i.p. injection twice daily. To activate TRPV1 visceral afferents, TRPV1-hM3Dq mice received vehicle or CNO daily for 7 days, by oral gavage. After 7 days of treatment, visceral pain was evaluated by colorectal distension and spinal cords tissues were harvested to measure microglial activation. Results Our data validated the nociceptor specific expression and function of the DREADD in TRPV1-Cre mice. Inhibition of TRPV1 visceral afferents in DSS TRPV1-hM4Di mice was able to prevent the colitis-induced microglial activation and thus reduce visceral hypersensitivity. In contrast, activation of TRPV1 visceral afferents in TRPV1-hM3Dq mice was sufficient to drive microglial activation in the absence of colitis. Analysis of the proalgesic mediators derived from activated TRPV1-hM3Dq neurons identified ATP as a key factor of microglial activation. Conclusions Overall, these data provide novel insights into the mechanistic understanding of the gut/brain axis in chronic visceral pain and suggest a role of purinergic signaling that could be harnessed for testing effective therapeutic approaches to relieve pain in IBD patients. Funding Agencies CCCACHRI (Alberta Children’s Hospital Research Institute) and CSM (Cumming School of Medicine) postdoctoral fellowship

Designer Drugs That Are Potent Inhibitors of CYP2D6

2002 ◽  
Vol 22 (3) ◽  
pp. 330-332 ◽  
Author(s):  
David Pritzker ◽  
Anish Kanungo ◽  
Tansel Kilicarslan ◽  
Rachel F. Tyndale ◽  
Edward M. Sellers
Keyword(s):  
Designer Drugs

Designer drugs: Review and implications for emergency management

2017 ◽  
Vol 37 (1) ◽  
pp. 94-101 ◽  
Author(s):  
A Pourmand ◽  
M Mazer-Amirshahi ◽  
S Chistov ◽  
A Li ◽  
M Park
Keyword(s):  
Emergency Management ◽  
Designer Drugs

Hypothesizing that designer drugs containing cathinones (“bath salts”) have profound neuro-inflammatory effects and dangerous neurotoxic response following human consumption

2013 ◽  
Vol 81 (3) ◽  
pp. 450-455 ◽  
Author(s):  
Kenneth Blum ◽  
M. Foster Olive ◽  
Kevin K.W. Wang ◽  
Marcelo Febo ◽  
Joan Borsten ◽  
...  
Keyword(s):  
Designer Drugs ◽  
Human Consumption ◽  
Bath Salts

Combatting Designer Drugs Head On

ChemViews ◽  
2012 ◽  
Author(s):  
Henry Sewall
Keyword(s):  
Designer Drugs

Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia

2021 ◽  
Author(s):  
Eric D. Melonakos ◽  
Morgan J. Siegmann ◽  
Charles Rey ◽  
Christopher O’Brien ◽  
Ksenia K. Nikolaeva ◽  
...  
Keyword(s):  
Recovery Time ◽  
Low Dose ◽  
Designer Drugs ◽  
Male Rats ◽  
Parabrachial Nucleus ◽  
High Dose ◽  
Median Difference ◽  
Delta Power ◽  
Calcium Calmodulin Dependent ◽  
Ketamine Anesthesia

Background Parabrachial nucleus excitation reduces cortical delta oscillation (0.5 to 4 Hz) power and recovery time associated with anesthetics that enhance γ-aminobutyric acid type A receptor action. The effects of parabrachial nucleus excitation on anesthetics with other molecular targets, such as dexmedetomidine and ketamine, remain unknown. The hypothesis was that parabrachial nucleus excitation would cause arousal during dexmedetomidine and ketamine anesthesia. Methods Designer Receptors Exclusively Activated by Designer Drugs were used to excite calcium/calmodulin–dependent protein kinase 2α–positive neurons in the parabrachial nucleus region of adult male rats without anesthesia (nine rats), with dexmedetomidine (low dose: 0.3 µg · kg−1 · min−1 for 45 min, eight rats; high dose: 4.5 µg · kg−1 · min−1 for 10 min, seven rats), or with ketamine (low dose: 2 mg · kg−1 · min−1 for 30 min, seven rats; high dose: 4 mg · kg−1 · min−1 for 15 min, eight rats). For control experiments (same rats and treatments), the Designer Receptors Exclusively Activated by Designer Drugs were not excited. The electroencephalogram and anesthesia recovery times were recorded and analyzed. Results Parabrachial nucleus excitation reduced delta power in the prefrontal electroencephalogram with low-dose dexmedetomidine for the 150-min analyzed period, excepting two brief periods (peak median bootstrapped difference [clozapine-N-oxide – saline] during dexmedetomidine infusion = −6.06 [99% CI = −12.36 to −1.48] dB, P = 0.007). However, parabrachial nucleus excitation was less effective at reducing delta power with high-dose dexmedetomidine and low- and high-dose ketamine (peak median bootstrapped differences during high-dose [dexmedetomidine, ketamine] infusions = [−1.93, −0.87] dB, 99% CI = [−4.16 to −0.56, −1.62 to −0.18] dB, P = [0.006, 0.019]; low-dose ketamine had no statistically significant decreases during the infusion). Recovery time differences with parabrachial nucleus excitation were not statistically significant for dexmedetomidine (median difference for [low, high] dose = [1.63, 11.01] min, 95% CI = [−20.06 to 14.14, −20.84 to 23.67] min, P = [0.945, 0.297]) nor low-dose ketamine (median difference = 12.82 [95% CI: −3.20 to 39.58] min, P = 0.109) but were significantly longer for high-dose ketamine (median difference = 11.38 [95% CI: 1.81 to 24.67] min, P = 0.016). Conclusions These results suggest that the effectiveness of parabrachial nucleus excitation to change the neurophysiologic and behavioral effects of anesthesia depends on the anesthetic’s molecular target. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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