QUINELORANE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H22N4
Molecular Weight	246.3513
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CCCN(CCC)[C@]1([H])CC3=C(C2)N=C(N)N=C3

InChI

InChIKey=TUFADSGTJUOBEH-ZWNOBZJWSA-N

InChI=1S/C14H22N4/c1-2-5-18-6-3-4-10-7-12-11(8-13(10)18)9-16-14(15)17-12/h9-10,13H,2-8H2,1H3,(H2,15,16,17)/t10-,13-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1673422 | https://www.ncbi.nlm.nih.gov/pubmed/1833778 | https://www.ncbi.nlm.nih.gov/pubmed/18579193

Quinelorane is an octahydropyrimido[4,5-g]quinolone derivative patented by American pharmaceutical company Eli Lilly and Co. as for the treatment anxiety, Parkinson's syndrome, depression, and hypertension. Quinelorane acts as an agonist of dopamine agonist for the D2 and D3 receptors. In preclinical studies Quinelorane (IM) treatment produced dose-dependent effects on male sexual responding. Penile erections and masturbation were markedly facilitated following treatment with either 2.5 or 5 micrograms/kg quinelorane. Higher doses of quinelorane (10 and 25 micrograms/kg) generally did not further augment sexual responding but rather resulted in a return in sexual responding to control vehicle levels. Quinelorane had a biphasic effect on yawning behavior of the monkeys with low doses (2.5 and 5 micrograms/kg) facilitating yawning and high doses (25 micrograms/kg) inhibiting yawning.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17976986	Agonist 2678		2.0 nM [EC50]
Dopamine D3 receptor 91 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17976986	Agonist 2678		1.0 nM [EC50]

PubMed

Title	Date	PubMed
Pharmacology of human dopamine D3 receptor expressed in a mammalian cell line: comparison with D2 receptor.	1992 Apr 10	1354163
Functional correlates of dopamine D3 receptor activation in the rat in vivo and their modulation by the selective antagonist, (+)-S 14297: 1. Activation of postsynaptic D3 receptors mediates hypothermia, whereas blockade of D2 receptors elicits prolactin secretion and catalepsy.	1995 Nov	7473180
Evidence to suggest that agonist modulation of hyperlocomotion is via post-synaptic dopamine D2 or D3 receptors.	1997 Jun	9225306
Nonlinear analysis of partial dopamine agonist effects on cAMP in C6 glioma cells.	2001 Jan-Feb	11489662
An investigation of the mechanisms responsible for acute fluoxetine-induced anxiogenic-like effects in mice.	2001 Jun	11485052
Influence of social isolation and 6-OHDA lesion on the effects of quinelorane.	2001 May-Jun	11420079
Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.	2001 Nov 30	11716810
In vivo characterization of basal amino acid levels in subregions of the rat nucleus accumbens: effect of a dopamine D(3)/D(2) agonist.	2001 Sep	11434978
Role of dopamine D2-like receptors in cocaine self-administration: studies with D2 receptor mutant mice and novel D2 receptor antagonists.	2002 Apr 1	11923462
Dopamine D1/5 receptor stimulation induces c-fos expression in the subthalamic nucleus: possible involvement of local D5 receptors.	2002 Jan	11860513
D2-like receptor-mediated inhibition of Na+-K+-ATPase activity is dependent on the opening of K+ channels.	2002 Jul	12060593
Deletion of CCK2 receptor in mice results in an upregulation of the endogenous opioid system.	2002 Mar 1	11880531
Piribedil enhances frontocortical and hippocampal release of acetylcholine in freely moving rats by blockade of alpha 2A-adrenoceptors: a dialysis comparison to talipexole and quinelorane in the absence of acetylcholinesterase inhibitors.	2003 Apr	12649387
Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity.	2003 Apr	12505882
Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in rats.	2003 Feb	12525958
Facilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice.	2003 Jun 16	12798264
The modulatory actions of dopamine D2/3 agonists and antagonists on the locomotor-activating effects of morphine and caffeine in mice.	2003 May	12873628
Effects of a dopamine D3 receptor ligand, BP 897, on acquisition and expression of food-, morphine-, and cocaine-induced conditioned place preference, and food-seeking behavior in rats.	2003 Nov	12915863
Dopaminergic modulation of behavioral states in mesopontine tegmentum: a reverse microdialysis study in freely moving cats.	2003 Nov 1	14655911
Gradient of dopamine responsiveness to dopamine receptor agonists in subregions of the rat nucleus accumbens.	2003 Sep 12	14519414
Effects of dopamine indirect agonists and selective D1-like and D2-like agonists and antagonists on cocaine self-administration and food maintained responding in rats.	2004	15464142
Quantification and pharmacological characterization of dialysate levels of noradrenaline in the striatum of freely-moving rats: release from adrenergic terminals and modulation by alpha2-autoreceptors.	2004 Dec 30	15589344
Modulation of the discriminative stimulus effects of mu opioid agonists in rats: II. Effects of dopamine D2/3 agonists.	2004 Feb	15075629
Modulation of the locomotor activating effects of the noncompetitive NMDA receptor antagonist MK801 by dopamine D2/3 receptor agonists in mice.	2004 Feb	14751459
Neuromodulation of the locomotor network by dopamine in the isolated spinal cord of newborn rat.	2004 Mar	15016090
Protection against cocaine toxicity in mice by the dopamine D3/D2 agonist R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol [(+)-PD 128,907].	2004 Mar	14711932
Blockade by the cannabinoid CB1 receptor antagonist, rimonabant (SR141716), of the potentiation by quinelorane of food-primed reinstatement of food-seeking behavior.	2004 May	14694354
Differential effects of dopaminergic agents on locomotor sensitisation and on the reinstatement of cocaine-seeking and food-seeking behaviour.	2004 Oct	15064914
Dopamine D3 receptor ligands modulate the acquisition of morphine-conditioned place preference.	2004 Sep	15095031
Physicochemical modulation of agonist-induced [35s]GTPgammaS binding: implications for coexistence of multiple functional conformations of dopamine D1-like receptors.	2005	16149770
Mapping the effects of the selective dopamine D2/D3 receptor agonist quinelorane using pharmacological magnetic resonance imaging.	2005	15893653
A reconfiguration of CaV2 Ca2+ channel current and its dopaminergic D2 modulation in developing neostriatal neurons.	2005 Dec	16120665
Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice.	2005 Feb	15494551
Delta-9-tetrahydrocannabinol differentially suppresses emesis versus enhanced locomotor activity produced by chemically diverse dopamine D2/D3 receptor agonists in the least shrew (Cryptotis parva).	2005 Jan	15652378
Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis.	2005 Jul	15723230
Perinatal exposure to low levels of the environmental antiandrogen vinclozolin alters sex-differentiated social play and sexual behaviors in the rat.	2005 Jun	15929892
Dopamine D3 modulation of locomotor activity and sleep in the nucleus accumbens and in lobules 9 and 10 of the cerebellum in the rat.	2005 Jun	15913875
D2-like receptors mediate the expulsion phase of ejaculation elicited by 8-hydroxy-2-(di-N-propylamino)tetralin in rats.	2006 Feb	16221741
Dopamine transporter (DAT) inhibitors alleviate specific parkinsonian deficits in monkeys: association with DAT occupancy in vivo.	2006 Nov	16885433
Effects of selective dopamine D1-like and D2-like agonists on prepulse inhibition of startle in inbred C3H/HeJ, SPRET/EiJ, and CAST/EiJ mice.	2007 Apr	17019570
Action of novel antipsychotics at human dopamine D3 receptors coupled to G protein and ERK1/2 activation.	2007 Aug	17588617
Yawning and hypothermia in rats: effects of dopamine D3 and D2 agonists and antagonists.	2007 Aug	17393143
Insulin replacement restores the behavioral effects of quinpirole and raclopride in streptozotocin-treated rats.	2007 Mar	17170311
Lack of self-administration of cocaine in dopamine D1 receptor knock-out mice.	2007 Nov 28	18045908
D2-like receptors in nucleus accumbens negatively modulate acetylcholine release in prefrontal cortex.	2007 Sep	17681559
Decrease of D2 receptor binding but increase in D2-stimulated G-protein activation, dopamine transporter binding and behavioural sensitization in brains of mice treated with a chronic escalating dose 'binge' cocaine administration paradigm.	2008 Aug	18671743
Lack of D2 receptor mediated regulation of dopamine synthesis in A11 diencephalospinal neurons in male and female mice.	2008 Jun 12	18462709
Quinelorane, a dopamine D3/D2 receptor agonist, reduces prepulse inhibition of startle and ventral pallidal GABA efflux: time course studies.	2008 Oct	18579193
Neural basis for a heritable phenotype: differences in the effects of apomorphine on startle gating and ventral pallidal GABA efflux in male Sprague-Dawley and Long-Evans rats.	2009 Dec	19756524
Penile erection and yawning induced by dopamine D2-like receptor agonists in rats: influence of strain and contribution of dopamine D2, but not D3 and D4 receptors.	2009 Jul	19584712

Patents

Sample Use Guides

In Vivo Use Guide

2.5 or 5 micrograms/kg

Route of Administration: Oral

Name

Type

Language

QUINELORANE

Official Name

English

quinelorane [INN]

Common Name

English

(-)-(5AR,9AR)-2-AMINO-5,5A,6,7,8,9,9A,10-OCTAHYDRO-6-PROPYLPYRIDO(2,3-G)QUINAZOLINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66884