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Personal profile

Research interests

Dr. Richard Mailman has had a decades-long interest in the design and discovery of novel dopamine receptor ligands.

The Mailman lab was also the first to discover, elaborate, and name (in 1994) the major pharmacology research front now called functional selectivity (how drugs acting at a single receptor differentially activate or block selected signaling pathways of that receptor).

Dr. Mailman's current research uses both dopamine D1 and D2 receptors as a model system and target for drug discovery. He is especially interested in the discovery of ligands with agonist properties at the D1 receptor, with data showing that D1 agonists can provide useful therapy in mid- and late-stage Parkinson’s disease, for improving deficits in cognition and memory, for ADHD, and even possibly for and Huntington’s disease. 

Dr. Mailman's current research in this area is focused on typical agonists with improved drugability, on functionally selective D1-like ligands, and the discovery of D1 or D5 selective ligands. The lab has recently identified a lead compound that is a potential clinical candidate and for which it has already demonstrated anti-Parkinson efficacy in non-human primates.

The lab's second focus is on functional selectivity of the D2 receptor. Here, they are interested in how small changes to drug-induced/selected conformations of the D2 receptor cause major differences in the signaling profiles of the receptor, and how resulting models may help design and discover functionally selective D2 ligands. 

The Mailman lab has played a major role in the understanding of aripiprazole (Abilify) pharmacology and in the path that brought it to the clinic. Moreover, the only D1 agonists currently available for clinical experimentation were discovered and developed by the Mailman group.

Dr. Mailman has active collaborations with the Parkinson’s disease research group at Penn State College of Medicine headed by Dr. Xuemei Huang.

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Dopamine Medicine & Life Sciences
Dopamine D1 Receptors Medicine & Life Sciences
Dopamine Agonists Medicine & Life Sciences
Dopamine Receptors Medicine & Life Sciences
Antipsychotic Agents Medicine & Life Sciences
Parkinson Disease Medicine & Life Sciences
Rats Chemical Compounds
Corpus Striatum Medicine & Life Sciences

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Projects 1975 2021

Molecular Probes
Dopamine D1 Receptors
Ligands
Single-Photon Emission-Computed Tomography
Catechols

Functional Selectivity: A Novel approach for CNS Drug Discovery

Mailman, R., Roth, B., Caron, M. G., Caron, M. G., Wetsel, W. & Jian, J.

National Institutes of Health

9/28/074/30/18

Project: Research project

Ligands
Dopamine D2 Receptors
Antipsychotic Agents
Schizophrenia
Signal Transduction
Dopamine D1 Receptors
Hemagglutinins
Arrestins
Arrestin
GTP-Binding Proteins
Dopamine Receptors
GTP-Binding Proteins
Adenylyl Cyclases
Dopamine
Lactotrophs

IMMUNE AND BRAIN STUDIES

Mailman, R. & Allen, A.

National Institutes of Health

12/8/8912/27/94

Project: Research project

Brain
Parturition
Haplorhini
Rodentia
Lithium

Research Output 1971 2019

1 Citation (Scopus)

Brain cholesterol metabolism and Parkinson's disease

Huang, X., Sterling, N. W., Du, G., Sun, D., Stetter, C., Kong, L., Zhu, Y., Neighbors, J., Lewis, M., Chen, H., Hohl, R. & Mailman, R., Mar 1 2019, In : Movement Disorders. 34, 3, p. 386-395 10 p.

Research output: Contribution to journalArticle

Parkinson Disease
Cholesterol
Brain
Odds Ratio
Logistic Models

Cancer and the Dopamine D2 Receptor: A Pharmacological Perspective

Weissenrieder, J. S., Neighbors, J., Mailman, R. & Hohl, R., Jul 1 2019, In : The Journal of pharmacology and experimental therapeutics. 370, 1, p. 111-126 16 p.

Research output: Contribution to journalArticle

Dopamine D2 Receptors
Pharmacology
Neoplasms
Ligands
Drug Therapy

Higher Hippocampal Mean Diffusivity Values in Asymptomatic Welders

Lee, E. Y., Flynn, M. R., Du, G., Lewis, M., Kong, L., Yanosky, J., Mailman, R. & Huang, X., Apr 1 2019, In : Toxicological Sciences. 168, 2, p. 486-496 11 p.

Research output: Contribution to journalArticle

Manganese
Alzheimer Disease
Hippocampus
Brain
Diffusion tensor imaging
10 Citations (Scopus)

Characterization of the neurochemical and behavioral effects of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor

Baladi, M. G., Forster, M. J., Gatch, M. B., Mailman, R., Hyman, D. L., Carter, L. P. & Janowsky, A., Aug 1 2018, In : Journal of Pharmacology and Experimental Therapeutics. 366, 2, p. 367-376 10 p.

Research output: Contribution to journalArticle

Dopamine Uptake Inhibitors
Narcolepsy
Obstructive Sleep Apnea
Inhibitory Concentration 50
Norepinephrine
1 Citation (Scopus)

D1 dopamine receptors intrinsic activity and functional selectivity affect working memory in prefrontal cortex

Yang, Y., Lee, S. M., Imamura, F., Gowda, K., Amin, S. & Mailman, R., Jan 1 2018, (Accepted/In press) In : Molecular Psychiatry.

Research output: Contribution to journalArticle

Arrestin
Prefrontal Cortex
Short-Term Memory
Dopamine
Adenylyl Cyclases