Disease relevance of Eltoprazine

• At postsynaptic 5-HT1A receptors mediating hypothermia, eltoprazine, WY 48,723, MDL 72832 and tandospirone are agonists, zalospirone is a partial agonist and (-)-tertatolol, WAY 100,135, MDL 73005 EF and SDZ 216-525 are antagonists [1].

Psychiatry related information on Eltoprazine

• Eltoprazine for aggression in schizophrenia and mental retardation [2].
• Dose-related suppression of REM sleep and PGO waves by the serotonin-1 agonist eltoprazine [3].
• In addition to REM suppression, eltoprazine produced other electroencephalographic changes: an increase in slow-wave sleep (S) percent without any change in overall wake (W) percent; an increase in electromyogram (EMG) amplitude; and a decrease in ponto-geniculo-occipital (PGO) wave activity [4].
• Wakefulness was unaffected by eltoprazine regardless of dose [3].
• The effects of eltoprazine (DU 28853) on exploratory behavior and conspecific social attraction were examined in four experiments [5].

High impact information on Eltoprazine

• A series of unsubstituted and substituted succinimido, maleimido, and glutarimidoethyl derivatives of eltoprazine (3) was synthesized and tested for affinity for the 5-HT1A receptor in rat brain homogenates [6].
• The virtual total suppression of REM sleep (0.4%, 4.0 mg/kg) and PGO wave activity (2 to 4 mg/kg) in exchange for increasing amounts of non-REM (NREM) slow-wave sleep was a dose-dependent function of the amount of eltoprazine administered [3].
• The serotonergic agonist, eltoprazine, behaved as a partial agonist (Emax = 52.7%) at RGlow membranes but virtually as a full agonist (Emax = 93.2%) at RGhigh membranes, relative to 5-HT (= 100%) [7].
• The eltoprazine cue partially generalized to the cues of the 5-HT1a agonists flesinoxan and buspirone, (m-CPP), the 5-HT1b/1c agonist 1,3-chlorophenyl-piperazine dihydrochloride and the 5-HT1c/2 antagonist mesulergine, and did not generalize to the 5-HT2/1c agonist DOI [8].
• In this study we report the effects of eltoprazine, a phenylpiperazine derivative with high affinity for 5-hydroxytryptamine1 (5HT1) binding sites, on membrane properties of hippocampal neurons [9].

Biological context of Eltoprazine

• Pharmacokinetics of eltoprazine in healthy male subjects after single dose oral and intravenous administration [10].
• Furthermore, GTP did not affect the competition for [125I]ICYP binding by the 5-HT1-antagonist methiothepin, whereas it did significantly reduce the displacement by eltoprazine, resulting in an almost twofold increase in IC50 values [11].
• The kinetics, safety and tolerability of eltoprazine hydrochloride were studied in an open, cross-over, partially randomised design after single oral (8 mg) and intravenous (3 and 8 mg) doses to 12 healthy male subjects [10].
• 8-OH-DPAT and flesinoxan (full agonists); ipsapirone (selective partial agonist) and eltoprazine (non selective partial agonist), all induced a dose-dependent reduction in core body temperature, which was maximal 30 min subsequent to administration [12].
• It was shown that the absorption of eltoprazine from the gastro-intestinal tract was complete, and that absolute bioavailability was 100% [13].

Anatomical context of Eltoprazine

• Within the amygdala, but not in other structures, the quantitative autoradiographic analysis of the 5-HT2C binding sites showed a differential effect: mianserin treatment induced a decrease in the number of these sites, while eltoprazine treatment resulted in an increase [14].
• Eltoprazine (1 microM) inhibits the forskolin stimulated c-AMP production in hippocampus slices of the rat, indicating an agonistic action on the 5-HT1A receptor [15].

Associations of Eltoprazine with other chemical compounds

• As TFMPP has a significantly lower affinity for 5-HT1A receptors than 8-OH-DPAT or eltoprazine, the lack of effect of TFMPP supports this view [16].
• The data indicate that the anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor sites and that this interaction is modulated by guanine nucleotides [11].
• Substitution for 8-OH-DPAT by eltoprazine and RU 24969, which does not occur in rats, provides in vivo support for the suggestion that the absence of a 5-HT1B receptor in the pigeon allows more complete expression of 5-HT1A-mediated effects [17].

Gene context of Eltoprazine

• Eltoprazine, a mixed 5-HT1A/B agonist, and meta-trifluoro-methylphenyl-piperazine HCl (TFMPP), a more selective 5-HT1B agonist, specifically decrease aggressive behavior in several animal species and situations in both sexes without detriment to other social, exploratory, or motoric activities [18].
• The pharmacological and anatomical data indicate that eltoprazine binds to 5-HT1A, 5-HT1B and to a lesser extent to 5-HT1C binding sites in the rat brain [19].
• In spite of this, neither mianserin- nor eltoprazine-treated rats displayed an alteration in the 5-HT2C receptor mRNA levels in the brain regions examined [14].
• The results suggest that the aggression-modulating effects of eltoprazine, as well as other drugs, may be mediated in part by their effects on normal olfactory function [20].

Analytical, diagnostic and therapeutic context of Eltoprazine

• We characterized the binding of radiolabelled eltoprazine in rat brain by autoradiography [11].
• Oral administration of eltoprazine (1 mg/kg) specifically reduced offensive aggression in both sham- and 5,7-DHT-lesioned animals, leaving social interest and exploration intact or even increasing it [21].
• The dose-proportionality and pharmacokinetics of eltoprazine HCl has been investigated after single oral doses of 5, 10, 20 mg (18 subjects) and 30 mg (12 subjects) in a partly randomized, cross-over design [22].

References