PMID: 1971308Jun 1, 1990Paper

trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenanthridine: a highly potent selective dopamine D1 full agonist

Journal of Medicinal Chemistry
W K BrewsterRichard B Mailman


trans-10,11-Dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a]phenan thridine (4a, dihydrexidine) has been found to be a highly potent and selective agonist of the dopamine D1 receptor in rat brain. Dihydrexidine had an EC50 of approximately 70 nM in activating dopamine-sensitive rat striatal adenylate cyclase and a maximal stimulation equal to or slightly greater than that produced by dopamine. Dihydrexidine had an IC50 of 12 nM in competing for [3H]SCH23390 (1a) binding sites in rat striatal homogenate, and of 120 nM versus [3H]spiperone. These data demonstrate that dihydroxidine has about ten-fold selectivity for D1/D2 receptors. More importantly, however, is the fact that dihydrexidine is a full agonist. Previously available agents, such as SKF38393 (1b), while being somewhat more selective for the D1 receptor, are only partial agonists. The isomeric cis-dihydroxybenzo[a]-phenanthridine neither stimulated cAMP synthesis nor inhibited the cAMP synthesis induced by dopamine. The cis isomer also lacked appreciable affinity for [3H]-1a binding sites. N-Methylation of the title compound decreased affinity for D1 sites about 7-8-fold and markedly decreased ability to stimulate adenylate cyclase. Addition of an N-n-propyl group reduced af...Continue Reading


Apr 1, 1995·Psychopharmacology·V J WattsR B Mailman
Jan 1, 1995·Journal of Neural Transmission. Parkinson's Disease and Dementia Section·M GosselW Danysz
Aug 3, 2005·Psychopharmacology·Mark R Wade, George G Nomikos
Apr 1, 2006·Psychopharmacology·Scott D Gleason, Jeffrey M Witkin
Jun 25, 1991·European Journal of Pharmacology·M P DeNinnoL Bednarz
Jul 19, 1991·European Journal of Pharmacology·J R TaylorR B Mailman
Dec 15, 1992·European Journal of Pharmacology·J W KebabianM Williams
Apr 22, 1993·European Journal of Pharmacology·J D KohliD E Nichols
Aug 3, 1993·European Journal of Pharmacology·V J WattsR B Mailman
Nov 19, 1991·Brain Research. Developmental Brain Research·M H TeicherR J Baldessarini
Mar 1, 1992·Neurochemistry International·J W KebabianK E Asin
Feb 5, 2004·Bioorganic & Medicinal Chemistry·Sing-Yuen SitRichard B Mailman
Sep 23, 1997·Pharmacology, Biochemistry, and Behavior·T D SteeleK W Locke
Feb 16, 2011·Chemical Communications : Chem Comm·Saumen Hajra, Sukanta Bar
Mar 13, 2009·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Peter M Lalley
Jul 31, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Daniel R RosellLarry J Siever
Nov 26, 2013·Neurobiology of Learning and Memory·Antony D AbrahamK Matthew Lattal
Mar 8, 2016·Biological Psychiatry·Amy F T ArnstenRichard B Mailman
Nov 26, 2008·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Julie A PrzybylaVal J Watts
Jul 22, 2008·Medicinal Research Reviews·Jing ZhangAo Zhang

❮ Previous
Next ❯

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.


Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.


Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.