Richard M. Van Rijn

Associate Professor of Medicinal Chemistry and Molecular Pharmacology
765-494-6461, 765-494-6564
Specialization: Neuropharmacology and drug discovery


B.S./M.S. (2002): Bio-pharmaceutical Sciences - Leiden University
Ph.D. (2007): Molecular Pharmacology - VU University Amsterdam
Postdoc. (2007-2013): Ernest Gallo Clinic and Research Center Department of Neurology - University of California San Francisco


In my laboratory we use innovative strategies and techniques to provide a better understanding of the molecular mechanism by which G-protein coupled receptors (GPCRs) function, propagate signal transduction and modulate behavior. GPCRs form the largest protein family in the human genome and are crucial in relaying extracellular information into the cell. GPCRs are involved in many diverse physiological responses, including light perception, taste, immune responses, cardiovascular activity and neurotransmission. Currently, 30-40% of all drugs, approved by the Federal Drug Administration, target GPCRs. New insights into how these receptors work have re-energized the study of these receptors. Specifically, we study biased receptor signaling and GPCR heteromerization and potential overlap of these concepts and their roles in (patho)-physiological responses. We frequently use the delta opioid receptor as model receptor for our studies. We use a combination of in vitro cell culture assays, with in vivo mouse behavioral paradigms and ex vivo assays to perform translational/pre-clinical research with the goal of proposing and developing new therapeutic drugs that may have better potency, efficacy and fewer side effects. Our main focus is on neurological disorders, with an emphasis on drug addiction and co-morbid mood and anxiety disorders as well as chronic pain conditions. Current projects involve investigations into the risk of the alcohol mixed energy drinks, the role of beta-arrestin dependent signaling in depression and anxiety disorders, the physiological function of opioid-dopamine interactions and alcohol withdrawal induced hyperalgesia.

Van Rijn Lab 2017
The Van Rijn lab: [Top from left to right] Arbaaz Mukadam, Ben Cummins, Rob Cassell, Maria Shelley, Richard van Rijn, Kendall Mores. [Bottom] Grace Mulia, Angel Lin, Haoyue Cui, Arryn Blaine, Anna Gutridge, Mee Jung Ko

Lab Members

Arryn Taylor Blaine (PULSe Graduate Student)
Alexander R. French (Post-Doctoral Research Associate)
Anna Marie Gutridge (Graduate Student)
Yazan J. Meqbil (Graduate Student)

Service and Engagement

Purdue Animal Care and Use committee member: 2015-present

MCMP Graduate admissions committee: 2015-present

Purdue University Life Sciences executive committee: 2017-present

Head of the Integrative Neuroscience training group: 2017-present  

College of Pharmacy Professional Program Admissions Committee: 2018-present


PHRM825: Integrated Pharmacotherapy I

PHRM844: Integrated Pharmacotherapy II

PHRM845: Integrated Pharmacotherapy III

PHRM316: Drug abuse/addiction education

Honors and Credentials

INRC Young Investigator Award (2021)

NIH/NCATS Aspire Reduction to Practice Challenge Prize (2021)     

NARSAD Young Investigator Award (2016)

K99/R00 Pathway to Independence Award (2011)


National Insitute on Alcohol Abuse and Alcoholism (R21AA026675)  9/1/2018 - 08/31/2020

The influence of alcohol on disseminated tumor cells dormancy

The goal of this proposal is to investigate how alcohol use can influence systemic tumor dormancy following breast cancer metastasis

Role: Co-PI (With Dr. Wendt)

National Insitute on Alcohol Abuse and Alcoholism (R21AA026949)  8/1/2018 - 07/31/2020

Opioidergic alkaloids from Mitragynia Speciosa (kratom) as novel treatment for alcohol use disorder

The goal of this proposal is to study the impact of kratom and kratom alkaloids on alcohol use and reward in mice

Role: PI

National Institute on Drug Abuse (R03DA045897) 04/01/2018-03/31/2020

Development of G-protein biased delta opioid receptor agonists for inflammatory pain

The goal of this proposal is to synthesize novel G-protein biased delta opioid receptors to treat acute inflammatory pain

Role: PI

National Insitute on Alcohol Abuse and Alcoholism (R01AA025368)  10/1/2017 - 09/31/2022

G-protein-, beta-arrestin- and ERK-signaling in alcohol use- and anxiety-disorders

The primary objective of this grant is to to study the role of ERK signaling induced by G-protein or beta-arrestin pathways in modulation of alcohol and anxiety behaviors.

Role: PI

Representative Publications

  1. Charkaborty S, Diberto J, Faouzi A, Bernhard SM, Gutridge AM, Ramsey S, Zhou Y, Provasi D, Nuthikattu N, Jilakia R, Nelson M, Asher W, Eans SO, Wilson LL, Chintala S, Filizola M, van Rijn RM, Margolis EB, Roth B, Javitch J, McLaughlin JP, Che T, Majumdar S, A novel mitragynine analog displays low efficacy mu opioid agonism at Gi/o subtypes and antinociception with attenuated adverse effects, J Med Chem, accepted
  2. Sharma KK1, Cassell RJ1, Meqbil YT1, Su H, Blaine AT, Cummins BR, Mores KL, Johnson D, Van Rijn RM, Altman RA, Modulating beta-arrestin-2 recruitment at the delta and mu opioid receptor, RCS Med Chem, accepted
  3. Ko MJ, Chiang T, Mukadam AM, Mulia, GE, Gutridge AM, Lin A, Chester JA, Van Rijn RM, β-arrestin-dependent ERK signaling reduces anxiety-like and conditioned fear-related behaviors in mice, Science Signaling, 2021, 14 (694): eaba0245 Cover article
  4. Farrokh Sharifi F, Meqbil YJ, Otte A, Gutridge AM, Blaine AT, Van Rijn RM, Park K, Engineering Quick- and Long-acting Naloxone Delivery Systems for Treating Opioid Overdose, Pharmacol Res, 2021, TBD, Accepted
  5. Ganzen L, Ko MJ, Zhang M, Xie R, Chen Y, Zhang L, James R, Mumm J, Van Rijn RM, Zhong W, Pang CP, Zhang M, Tsujikawa M, Leung YF, Drug Screening with Zebrafish Visual Behavior Identifies Carvedilol as a Potential Treatment for Retinitis Pigmentosa, Scientific Reports, 2021, 11, 11432
  6. Creed SM1, Gutridge AM1, Argade MD, Hennessy MR, Brent Friesen JJB, Pauli GF, van Rijn RM#, Riley AP#, Isolation and Pharmacological Characterization of six Opioidergic Picralima nitida Alkaloids, J Natural products, 2021, 84(1):71-80
  7. Bertels Z, Witkowski W, Asif S, Siegersma K, Van Rijn RM, Pradhan AA, A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia, Headache, 2021, 61(1): 170-178
  8. Ding Z, Knipp GT, Van Rijn RM, Chester JA, Watts VJ, The CUL3/neddylation inhibitor MLN4924 reduces inflammatory pain allodynia and ethanol-induced locomotor sensitization in mice, Behavioural Brain Research, 2021, 399, 113051
  9. 1Gutridge AM, 1Robins MT, 1Cassel RJ, 1Uprety R, Mores KL, Ko MJ, Pasternak GM, Majumdar S, Van Rijn RM, G protein-biased kratom-alkaloids and synthetic carfentanil-amide opioids as potential treatment for alcohol use disorder, Br J Pharmacol, 2020, 177(7): 1497-1513
  10. 1Cassell RJ, 1Sharma KK, Su H, Cummins BR, Cui H, Mores KL, Blaine AT, Altman RA#, Van Rijn RM#, The Meta-Position of Phe4 in Leu-Enkephalin Regulates Potency, Selectivity, Functional Activity, and Bias at the Delta and Mu Opioid Receptors, Molecules (Special issue Opioids and Their Receptors: Present and Emerging Concepts in Opioid Drug Discovery), 2019, 24 (4542): 1-15, PMID: 31842282, PMC6943441,
  11. Cai B, Kim D, Akhand S, Sun Y, Cassell RJ, Alpsoy A, Dykhuizen EC, Van Rijn RM, Wendt MK, Krusemark CJ, Selection of DNA-encoded libraries to protein targets within and on living cells, J Am Chem Soc, 2019, 141:17057-17061
  12. 1Mores KL, 1Cummins BR, Cassell RJ, Van Rijn RM, A review of the therapeutic potential of recently developed G protein-biased kappa agonists, Front Pharmacol, 2019, 10 (407):1-14
  13. 1Ko MJ, 1Mulia G, Van Rijn RM. Commonly used anesthesia/euthanasia methods for brain collection differentially impact MAPK activity in male and female C57BL/6 mice, Front Cell Neurosci, 2019, 13 (96):1-10
  14. Robins MT, Blaine AT, Ha JE, Brewster A, Van Rijn RM, Repeated Use of the Psychoactive Substance Ethylphenidate Impacts Neurochemistry and Reward Learning in Adolescent Male and Female Mice. Front Neurosci,  2019, 13 (124): 1-14
  15. 1Ko MJ, 1Ganzen L, Coskun E, Mukadam AA, Lueng YF, Van Rijn RM, Critical evaluation of TRPA1-mediated locomotive behavior in zebrafish as a screening tool for novel anti-nociceptive drug discovery. Sci Rep, 2019, 9 (2430): 1-11
  16. 1Cassell RJ, 1Mores KL, Zerfas BL, AHA Abdallah, Lill MA, Trader DJ, Van Rijn RM, Rubsicolins are naturally occurring G-protein-biased delta opioid receptor peptide, Eur Neuropsychopharmacol, 2019, 29(3): 450-456 
  17. Mores KL, Cassell RJ, van Rijn RM, arrestin recruitment and biased signaling by G protein-coupled receptor heteromers. Neuropharmacology (Special issue on Brain Heteroreceptor complexes in Health and Disease), accepted for publication,
  18. Kaur J, Soto-Velasquez M, Ding Z, Van Rijn RM, Watts VJ, Flaherty DP, Optimization of a 1,3,4-oxadiazole series for inhibition of adenylyl cyclase 1 and 8 for the treatment of chronic pain, 2019, Eur J Med Chem, 162, 565-585
  19. Robins MT, Chiang T, Mores, KL, Alongkronrusmee D, Van Rijn RM, Critical role for Gi-protein activity in the dorsal striatum in the reduction of voluntary alcohol intake in C57Bl/6 mice, 2018, Front. Psychiatry (Special topics in opioid research), 9 (112): 1-14.
  20. Robins MT, Chiang T, Berry JN, Ko MJ, Ha JE, Van Rijn RM, Behavioral characterization of b-arrestin 1 knockout mice in anxiety-like and alcohol behaviors, 2018, Front. Behav. Neurosci., 12 (54): 1-11
  21. Márquez-Gómez R, Robins MT, Gutiérrez-Rodelo C, Arias, JM, Olivares-Reyes JA, Van Rijn RM, Arias-Montaño JA, Functional histamine H3 and adenosine A2A receptor heteromers in recombinant cells and rat striatum, 2018, Pharmacol. Res., 129: 515-525, PMID: 29217157
  22. Brust TF, Alongkronrusmee D, Soto-Velasquez M, Baldwin TA, Ye Z, Dai, M, Dessauer CW, Van Rijn RM, Watts VJ, Identification of a selective small molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties, 2017, Science Signal, 10 (467): eaah5381, PMID:28223412.
  23. Zeng L, Alongkronrusmee D, Van Rijn RM, An integrative perspective on diabetic, alcoholic and drug-induced neuropathic pain, 2017, J Pain Res, 10: 219-228 PMID:28176937, PMC5268333. Noteworthy designation, highly accessed designation,
  24. Alongkronrusmee D, Chiang T, Van Rijn RM, Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice. 2016, Drug Alcohol Depend, 167:190-198 PMID: 27567436
  25. Yang S, Ben-Shalom R, Ahn M, Liptak AT, van Rijn RM, Whistler JL, Bender KJ, Beta-Arrestin-dependent dopaminergic regulation of calcium channel activity in the axon initial segment, 2016, Cell Rep, 16 (6), 1518-1526 PMID: 27452469, PMC5074334
  26. Robins MT, Lu J, Van Rijn RM, Unique behavioral and neurochemical effects induced by repeated adolescent consumption of caffeine-mixed alcohol in C57BL/6 mice, 2016, PLoS One, 11(7):e0158189 PMID: 27380261, PMC4933367, Top 1% of most downloaded articles of the year (out of 22,000)
  27. Robins MT, DeFriel JN, Van Rijn RM, adolescent intake of caffeinated energy drinks does not affect adult alcohol consumption in C57BL/6 and BALB/c mice, 2016, Alcohol, 54, 1-9, PMID:27565749
  28. Chiang T, Sansuk K, Van Rijn RM, β-arrestin 2 dependence of delta opioid receptor agonists is correlated with alcohol intake., Br. J Pharmacol, 2016, 173, 332-343, PMID:26507558, PMC4940619
  29. Van Rijn RM#, DeFriel JN, Whistler JL, Pharmacological traits of delta opioid receptors: pitfalls or opportunities, Psychopharmacol, 2013, 228(1), 1-18, #corresponding author, PMID:23649885, PMC3679311
  30. Milan-Lobo L, Enquist JE, Van Rijn RM, Whistler JL, anti-analgesic effect of the mu/delta opioid receptor-heteromer revealed by ligand-biased antagonism, 2013, PLoS One, 8(3): e58362, PMID:23554887, PMC3598907
  31. Van Rijn RM#, Harvey JH, Brissett DI, DeFriel JN, Whistler JL, Novel screening assay for the selective detection of G protein-coupled receptor heteromer signaling, 2013, J Pharmacol Exp Ther, 334(1):179-188, #corresponding author, PMID:23097213, PMC3533407, Highlighted paper
  32. Van Rijn RM#, Brissett DI, Whistler JL, Distinctive modulation of ethanol place preference by delta opioid receptor selective agonists, Drug Alcohol Depend, 2012, 122(1-2):156-159  #corresponding author, PMID:22018601, PMC3279630
  33. Brissett DI, Whistler JL, Van Rijn RM#, Contribution of mu and delta opioid receptors to the pharmacological profile of kappa opioid receptor subtypes, Eur. J Pain, 2012, 16 (3): 327-337. #corresponding author, PMID:22337177, PMC4086711
  34. Van Rijn RM, Brissett DI, Whistler JL, Emergence of functional spinal delta-mu opioid receptors heteromers after chronic ethanol exposure, Biol Psychiatry, 2012, 71:232-238, PMID:21889123, PMC4086708
  35. Van Rijn RM, Brissett DI, Whistler JL, Dual efficacy of delta opioid selective ligands for ethanol drinking and anxiety, J Pharmacol Exp Ther, 2010, 335 (1):133-139, PMID:20605909, PMC2957775
  36. Van Rijn RM, Rhee IK, Verpoorte R, Isolation of acetylcholinesterase inhibitory alkaloids from Nerine Bowdenii, Nat. Prod. Res, 2010, 24 (3):222-225, PMID:20140801
  37. Van Rijn RM, Whistler JL, Waldhoer M, Opioid receptor heteromer-specific trafficking and pharmacology, Curr Opin Pharmacol, 2010, 10:73-79, PMID:19846340, PMC2900797
  38. Van Rijn RM, Whistler JL. The delta-1 opioid receptor is a heterodimer that opposes the actions of the delta-2 receptor on alcohol intake, Biol. Psychiatry, 2009, 66:777-784, PMID:19576572, PMC2757485
  39. He L, Kim J, Ou C, McFadden W, van Rijn RM, Whistler JL, Methadone antinociception is dependent on peripheral opioid receptors, J Pain, 2009, 10 (4):369-379, PMID:19327642, PMC2952445
  40. Van Rijn RM, Whistler JL, The only way is up: preventing opioid tolerance by promoting cell surface expression of MOR-DOR heterodimers? Mol. Interv, 2008, 8 (6): 277-280, PMID:19144899
  41. Van Rijn RM, van Marle A, Chazot PL, Langemijer E, Qin Y, Shenton FC, Lim HD, Zuiderveld OP, Sansuk K, Dy M, Smit MJ, Tensen CP, Bakker RA, Leurs R, Cloning and characterization of dominant negative splice variants of the human histamine H4 receptor, Biochem J, 2008, 414 (1):121-131, PMID:18452403
  42. Van Rijn RM, Chazot PL, Shenton FC, Sansuk K, Bakker RA, Leurs R, Oligomerization of recombinant and endogenously expressed human histamine H4 receptors, Mol. Pharmacol. 2006, 70(2):604-15, PMID: 16645125
  43. Bakker RA, Lozada AF, van Marle A, Shenton FC, Drutel G, Karlstedt K, Hoffmann M, Lintunen M, Yamamoto Y, van Rijn RM, Chazot PL, Panula P, Leurs R, Discovery of naturally occurring splice variants of the rat histamine H3 receptor that act as dominant negatives, Mol. Pharmacol, 2006, 69(4):1194-206, PMID:16415177
  44. Lim, HD1 and Van Rijn RM1, Ling P, Bakker RA, Thurmond RL, Leurs R., Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005, 4(3):1310-21. 1shared first author, PMID:15947036 >300 citations
  45. Terzioglu N, van Rijn RM, Bakker RA, De Esch IJ, Leurs R., Synthesis and structure-activity relationships of indole and benzimidazole piperazines as histamine H4 receptor antagonists, Bioorg Med Chem Lett. 2004, 14(21):5251-6, PMID:15454206 >100 citations
  46. Rhee IK, van Rijn RM, Verpoorte R., Qualitative determination of false-positive effects in the acetylcholinesterase assay using thin layer chromatography, Phytochem Anal, 2003, 14(3):127-31, PMID: 12793457 >100 citation

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