Disease relevance of Pirenperone

• Mianserin (10 mg/kg) and pirenperone (0.03 mg/kg) also selectively antagonized hyperthermia induced by MK-212 [1].
• A low dose of pirenperone was also effective in blocking withdrawal-induced hypothermia [2].
• The effects of the 5-HT2 antagonist pirenperone on temperature preference were observed 1 hr after injection in mice aged 3, 5 and 7 days and at doses of 0.16, 0.48 and 1.6 mg/kg body weight [3].

Psychiatry related information on Pirenperone

• In view of previous results indicating that the panic-promoting drug yohimbine increases flight/escape reactions and that the panicolytic compound alprazolam reduces these responses, we tentatively suggest that the preferential 5-HT2A receptor antagonist pirenperone may have some efficacy in improving panic attacks [4].
• Pilot study of a specific serotonergic antagonist, pirenperone, in the treatment of anxiety disorders [5].

High impact information on Pirenperone

• By contrast, two serotonergic agents that do not meet the criteria were found to be inactive at the 5-HT3 receptor binding site (i.e., ipsapirone and pirenperone, KI values greater than 1000 nM) [6].
• Several 5-HT2 selective receptor antagonists (spiperone, cyproheptadine, pirenperone) competitively inhibited responses to 5-HT [7].
• The 5-HT1A receptor antagonist NAN 190 (0.2-0.8 mg/kg), the 5-HT2A/2C receptor antagonist LY 53857 (0.5-4 mg/kg) and the 5-HT/DA receptor antagonist pirenperone (0.5-4 mg/kg) neither substituted for nor enhanced cocaine; however, pirenperone but not NAN 190 or LY 53857 partially blocked the cocaine (10 mg/kg) response [8].
• The selective serotonin type-2 (S2) receptor blocker pirenperone (0.24 mg/kg, SC) attenuates morphine-produced tail-flick antinociception in intact rats, but not in rats with transected spinal cords [9].
• Selective effects of pirenperone on analgesia produced by morphine or electrical stimulation at sites in the nucleus raphe magnus and periaqueductal gray [10].

Biological context of Pirenperone

• Both effects (down-regulation and WDS) were prevented by the 5-HT2 receptor antagonist, pirenperone [11].
• In Experiment 3, both 150 micrograms/kg pirenperone and 3 mg/kg of the 5-HT agonist quipazine produced significant inhibition of male sexual behavior; however, when co-administered, inhibitory effects of each drug were significantly attenuated [12].
• Pirenperone effects on temperature preference and body temperature in maturing mice [13].
• Thermoregulatory effects of the selective 5-HT2 antagonist pirenperone were studied 1 hr after IP injection in mice aged 1, 3, 5, 7 and 10 days postpartum [13].

Anatomical context of Pirenperone

• We now report that pirenperone markedly stimulates prolactin (PRL) secretion in vivo at low doses and blocks the dopamine (DA)-induced inhibition of PRL release from rat pituitary glands in vitro, suggesting it acts as an antagonist at DA2 receptors in the anterior pituitary gland [14].
• Because pirenperone easily enters the central nervous system whereas ketanserin does not, these results indicate the involvement of central S2 receptors in morphine-induced antinociception [15].

Associations of Pirenperone with other chemical compounds

• The newly synthesized compound and putative 5-HT2 antagonist ritanserin, but not the structurally related compound R 56413, resembles pirenperone in that it acts as a pure antagonist in an LSD-saline drug discrimination assay in the rat [16].
• Pirenperone, which is chemically related to ketanserin, has been reported to be a selective serotonin2 (5-HT2) antagonist and a specific d-LSD antagonist [14].
• The quipazine-induced increase in serum corticosterone was antagonized by 17 different serotonin antagonists; of these, MDL 11939, pirenperone, setoperone, mianserin, LY 281067, ketanserin, ritanserin and clozapine have relatively selective affinity for the 5-HT2 subtype of receptor [17].
• [3H]Ketanserin binding sites from the soluble extract showed the binding characteristics of S2-receptors: potent 5HT antagonists like pirenperone, methysergide and pipamperone competed for [3H]ketanserin binding at nanomolar concentrations [18].
• In other experiments, the peripheral serotonin antagonist BW 501C was not able to prevent elevated Tpref produced by 5-HTP, although the specific 5-HT2 antagonist pirenperone, which reaches the CNS as well as the periphery, blocks the 5-HTP elevation of Tpref [19].

Gene context of Pirenperone

• The 5-HT2A receptor antagonist pirenperone did not provide significant indication of an anxiolytic effect on predator assessment activity and postpredator potentiation of contextual defense responses, and had negligible influence on antipredator defensive behavior [4].
• Tests of antagonism of stimulus control were conducted using the 5-HT1A antagonists (+/-)-pindolol and WAY-100635, and the 5-HT2 receptor antagonist pirenperone [20].
• 5-HT1A agonists modulate mouse antipredator defensive behavior differently from the 5-HT2A antagonist pirenperone [4].
• Pirenperone did not alter the rate of 5-HT synthesis in the rat brain [21].
• Effects of pirenperone and ketanserin on rat prolactin secretion in vivo and in vitro [14].

Analytical, diagnostic and therapeutic context of Pirenperone

• Pirenperone does not attenuate morphine analgesia in spinal rats [9].
• Comparable effects of pirenperone were observed when analgesia was produced by electrical stimulation of the NRM [10].
• The head-twitch response to intraperitoneal injection of 5-hydroxytryptophan in the rat: antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD antagonist [22].

References