Cardiovascular and Subjective Effects of the Novel Adenosine A(2A) Receptor Antagonist SYN115 in Cocaine Dependent Individuals

Overview

Journal J Addict Res Ther

Date 2012 Aug 21

PMID 22905331

Citations 5

Authors

Sd Lane

Ce Green

Jl Steinberg

L Ma

Jm Schmitz

N Rathnayaka

Sd Bandak

S Ferre

Fg Moeller

Affiliations

Soon will be listed here.

Abstract

A(2A) receptor antagonists have been proposed as therapeutic tools for dopaminergically-relevant diseases, including Parkinson's disease and substance dependence. The acute subjective and cardiovascular effects of a novel, selective adenosine A(2A) receptor antagonist (SYN115) were examined. Across an 8-hour experimental testing day, 22 non-treatment seeking cocaine-dependent subjects received either placebo capsules (PO) at both the AM and PM dosing times (Plc/Plc, N = 9), or placebo in the AM and 100 mg SYN115 in the PM (Plc/SYN115, N =13). Cardiovascular measures (HR, BP) were obtained across the test day, and subjective effects (ARCI, VAS) were obtained once before and once after the AM and PM doses (four time points total). There were no between-group effects on cardiovascular function, however subjective effects consistent with stimulation were observed on the VAS scales in the SYN115 group. In cocaine-dependent subjects, SYN115 may produce stimulant-like effects through a unique mechanism of action. Due to known monoamine dysfunction related to chronic cocaine use, these effects may be specific to this population relative to healthy control or other patient populations.

Citing Articles

Pathophysiological Role and Medicinal Chemistry of A Adenosine Receptor Antagonists in Alzheimer's Disease.

Merighi S, Borea P, Varani K, Vincenzi F, Travagli A, Nigro M Molecules. 2022; 27(9).

PMID: 35566035 PMC: 9102440. DOI: 10.3390/molecules27092680.

The Role of Adenosine Receptors in Psychostimulant Addiction.

Ballesteros-Yanez I, Castillo C, Merighi S, Gessi S Front Pharmacol. 2018; 8:985.

PMID: 29375384 PMC: 5767594. DOI: 10.3389/fphar.2017.00985.

Adenosine A1 and A2A Receptors in the Brain: Current Research and Their Role in Neurodegeneration.

Stockwell J, Jakova E, Cayabyab F Molecules. 2017; 22(4).

PMID: 28441750 PMC: 6154612. DOI: 10.3390/molecules22040676.

Comparison of Caffeine and d-amphetamine in Cocaine-Dependent Subjects: Differential Outcomes on Subjective and Cardiovascular Effects, Reward Learning, and Salivary Paraxanthine.

Lane S, Green C, Schmitz J, Rathnayaka N, Fang W, Ferre S J Addict Res Ther. 2014; 5(2):176.

PMID: 25414797 PMC: 4235768. DOI: 10.4172/2155-6105.1000176.

Structure-based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates.

Jacobson K J Med Chem. 2013; 56(10):3749-67.

PMID: 23597047 PMC: 3701956. DOI: 10.1021/jm400422s.

References

Jasinski D, Henningfield J . Human abuse liability assessment by measurement of subjective and physiological effects. NIDA Res Monogr. 1989; 92:73-100. View

Sigmon S, Griffiths R . Caffeine choice prospectively predicts positive subjective effects of caffeine and d-amphetamine. Drug Alcohol Depend. 2011; 118(2-3):341-8. PMC: 3188327. DOI: 10.1016/j.drugalcdep.2011.04.018. View

Heil S, Holmes H, Bickel W, Higgins S, Badger G, Laws H . Comparison of the subjective, physiological, and psychomotor effects of atomoxetine and methylphenidate in light drug users. Drug Alcohol Depend. 2002; 67(2):149-56. DOI: 10.1016/s0376-8716(02)00053-4. View

Mizuno Y, Hasegawa K, Kondo T, Kuno S, Yamamoto M . Clinical efficacy of istradefylline (KW-6002) in Parkinson's disease: a randomized, controlled study. Mov Disord. 2010; 25(10):1437-43. DOI: 10.1002/mds.23107. View

Schmitz J, Mooney M, Moeller F, Stotts A, Green C, Grabowski J . Levodopa pharmacotherapy for cocaine dependence: choosing the optimal behavioral therapy platform. Drug Alcohol Depend. 2008; 94(1-3):142-50. PMC: 2293271. DOI: 10.1016/j.drugalcdep.2007.11.004. View

Nikolaus S, Antke C, Kley K, Poeppel T, Hautzel H, Schmidt D . Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans. Rev Neurosci. 2008; 18(6):439-72. DOI: 10.1515/revneuro.2007.18.6.439. View

Ferre S . Role of the central ascending neurotransmitter systems in the psychostimulant effects of caffeine. J Alzheimers Dis. 2010; 20 Suppl 1:S35-49. PMC: 9361505. DOI: 10.3233/JAD-2010-1400. View

FISCHMAN M . Relationship between self-reported drug effects and their reinforcing effects: studies with stimulant drugs. NIDA Res Monogr. 1989; 92:211-30. View

Ferre S, Quiroz C, Orru M, Guitart X, Navarro G, Cortes A . Adenosine A(2A) Receptors and A(2A) Receptor Heteromers as Key Players in Striatal Function. Front Neuroanat. 2011; 5:36. PMC: 3118889. DOI: 10.3389/fnana.2011.00036. View

10.

Moeller F, Schmitz J, Herin D, Kjome K . Use of stimulants to treat cocaine and methamphetamine abuse. Curr Psychiatry Rep. 2008; 10(5):385-91. PMC: 9157609. DOI: 10.1007/s11920-008-0062-x. View

11.

Garrett B, Griffiths R . Intravenous nicotine and caffeine: subjective and physiological effects in cocaine abusers. J Pharmacol Exp Ther. 2001; 296(2):486-94. View

12.

Jenner P, Mori A, Hauser R, Morelli M, Fredholm B, Chen J . Adenosine, adenosine A 2A antagonists, and Parkinson's disease. Parkinsonism Relat Disord. 2009; 15(6):406-13. DOI: 10.1016/j.parkreldis.2008.12.006. View

13.

Schiffmann S, Fisone G, Moresco R, Cunha R, Ferre S . Adenosine A2A receptors and basal ganglia physiology. Prog Neurobiol. 2007; 83(5):277-92. PMC: 2148496. DOI: 10.1016/j.pneurobio.2007.05.001. View

14.

Harper L, Beckett S, Marsden C, McCreary A, Alexander S . Effects of the A 2A adenosine receptor antagonist KW6002 in the nucleus accumbens in vitro and in vivo. Pharmacol Biochem Behav. 2006; 83(1):114-21. DOI: 10.1016/j.pbb.2005.12.014. View

15.

Justinova Z, Ferre S, Segal P, Antoniou K, Solinas M, Pappas L . Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. J Pharmacol Exp Ther. 2003; 307(3):977-86. DOI: 10.1124/jpet.103.056762. View

16.

Herin D, Rush C, Grabowski J . Agonist-like pharmacotherapy for stimulant dependence: preclinical, human laboratory, and clinical studies. Ann N Y Acad Sci. 2010; 1187:76-100. DOI: 10.1111/j.1749-6632.2009.05145.x. View

17.

Varty G, Hodgson R, Pond A, Grzelak M, Parker E, Hunter J . The effects of adenosine A2A receptor antagonists on haloperidol-induced movement disorders in primates. Psychopharmacology (Berl). 2008; 200(3):393-401. DOI: 10.1007/s00213-008-1214-8. View

18.

Kanda T, Jackson M, Smith L, Pearce R, Nakamura J, Kase H . Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol. 1998; 43(4):507-13. DOI: 10.1002/ana.410430415. View

19.

Martin W, SLOAN J, SAPIRA J, Jasinski D . Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther. 1971; 12(2):245-58. DOI: 10.1002/cpt1971122part1245. View

20.

Martinez D, Broft A, Foltin R, Slifstein M, Hwang D, Huang Y . Cocaine dependence and d2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior. Neuropsychopharmacology. 2004; 29(6):1190-202. DOI: 10.1038/sj.npp.1300420. View