Disease relevance of CINANSERIN

• BOL and cinanserin treatment 5 minutes after the onset of ischemia was beneficial because neurologic improvement was permanent, and pretreatment with these drugs also markedly reduced damage [1].
• The antiviral activity of cinanserin was further evaluated in tissue culture assays, namely, a replicon system based on HCoV-229E and quantitative test assays with infectious SARS-CoV and HCoV-229E [2].
• Binding of both cinanserin and its hydrochloride to bacterially expressed 3CLpro of SARS-CoV and the related human coronavirus 229E (HCoV-229E) was demonstrated by surface plasmon resonance technology [2].
• Cinanserin is an inhibitor of the 3C-like proteinase of severe acute respiratory syndrome coronavirus and strongly reduces virus replication in vitro [2].
• S2 antagonists inhibited limb (arrhythmic and asynchronous) and axial (truncal) myoclonus in a dose-dependent manner in the rank order of potency: pirenperone greater than pipamperone greater than ketanserin = cinanserin [3].

Psychiatry related information on CINANSERIN

• The antagonists methiothepin and cinanserin only produced decreases in locomotor activity which did not appear to be related to the peak in activity [4].

High impact information on CINANSERIN

• Specific 125I-SCH 23982 binding was displaced by the selective D1 antagonists SCH 23390 (IC50 = 90 pM) and cis-flupenthixol (IC50 = 200 pM) and the D1 agonist SKF 38393 (IC50 = 110 nM) but not by D2-selective ligands (I-sulpiride, LY 171555) or the S2 antagonist cinanserin [5].
• The specific binding (defined by the difference in 3H-DOB binding in the presence and absence of 10(-6) M cinanserin, a potent and specific 5-HT2 antagonist) displayed high affinity (KD = 4.1 X 10(-10) M) and saturability with a Bmax of 17.9 fmol/mg of protein [6].
• 5-Hydroxytryptamine changes the shape of rat blood platelets by combination with a cinanserin-sensitive receptor which is not associated with the active uptake of 5-hydroxytryptamine [7].
• The 5-HT reuptake inhibitor fluoxetine enhanced the occurrence and severity of convulsions produced by 100 mg/kg (-) cocaine, while the 5-HT2 receptor antagonists cinanserin, ketanserin and pirenperone antagonized cocaine-induced convulsions in a dose-dependent manner [8].
• In contrast, the PBG excitations were unaffected by the 5-HT2 receptor antagonist, cinanserin (2/2), and the selective 5-HT1A receptor antagonist, WAY- 100802 (6/6) [9].

Chemical compound and disease context of CINANSERIN

• Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT [10].
• Pirenperone at 0.32 and 1.0 mg/kg, cinanserin 10 mg/kg and ritanserin 3.2 mg/kg administered i.p. immediately after blood flow reperfusion significantly reduced the increase in errors expected to occur 24 h after the 5 min of ischemia [11].
• However, pretreatment with either methysergide or cinanserin not only failed to inhibit tryptamine's potentiation of nociception, but actually enhanced the hyperalgesia produced by tryptamine [12].
• When 2.5 mg/kg cinanserin, a drug that antagonizes postsynaptic serotonergic receptors, was coadministered with a higher (95 mg/kg) dose of cocaine, the time of onset of status epilepticus was significantly increased, whereas lethality was reduced [13].

Biological context of CINANSERIN

• Regional and Scatchard analyses both clearly revealed that, in rat brain, at least two populations of binding sites were labelled by [3H]5-HT; however, high affinity binding sites (K(D) = 1.90 nM, Bmax = 0.188 pmoles/mg protein) could apparently be differentiated from the others by the action of 5 nM cinanserin [14].
• Two injections of the 5-HT2 receptor antagonist cinanserin (30 nmol/0.5 microliter) in the paraventricular nucleus of the hypothalamus completely reversed the effect of stress on food intake [15].
• This increase of blood pressure was blocked by pretreatment with cinanserin [16].
• In both protocols, cinanserin had no effect on ischemic regional blood flow or peripheral hemodynamics [17].
• Pretreatment with the 5-hydroxytryptaminergic receptor blockers cinanserin, cyproheptadine or D-2-bromolysergic acid diethylamide markedly attenuated the effects of fenfluramine but only slightly influenced the responses to PCA [18].

Anatomical context of CINANSERIN

• Moreover, the antinociceptive effect induced by 5-hydroxytryptamine administered into nucleus accumbens could be blocked by naloxone injected into the same site, whereas the antinociception elicited by intra-accumbens injection of [D-Ala2,D-Leu5]enkephalin was not affected by cinanserin, a 5-hydroxytryptamine blocking agent [19].
• Cinanserin (2-4 mg/kg) antagonize the inhibition of phrenic nerve activity [20].
• In synaptic membranes prepared from whole rat brain, cinanserin produced a relatively shallow inhibition curve of [3H] 5-HT binding with Hill slope of 0.68, as compared with that observed in the [3H]spiperone binding (Hill slope = 0.99) [14].
• Proceedings: The effects of cinanserin and phentolamine applied by microiontophoresis in the spinal cord [21].
• Inhibition of sympathetic activity by 5MeODMT is also reversed during 50 Hz carotid sinus nerve stimulation, but is unaltered by hypercapnia, hyperthermia or cinanserin [20].

Associations of CINANSERIN with other chemical compounds

• The 5-HT2 antagonists cyproheptadine, cinanserin, ritanserin, and ketanserin increased the rate of tactile startle habituation without affecting initial levels of reactivity [22].
• In membrane preparations of superior colliculus of the rat, the binding of [3H]spiperone (0.15 nM) was displaced by the incorporation of (+)-butaclamol, haloperidol, apomorphine and (+/-)-sulpiride, but not by (-)-butaclamol, prazosin, propranolol, ketanserin or cinanserin [23].
• These observations suggest cyproheptadine, pizotyline, methysergide, lysergic acid diethylamide, mianserin and cinanserin are agonists at the 5-HT1 receptor in the l-5-HTP discrimination and antagonists at a 5-HT2 receptor in the quipazine discrimination in pigeons [24].
• Co-incubation with increasing concentrations of several well-known 5-HT2-selective drugs, such as pirenperone, cinanserin and ketanserin, resulted in an inhibition of the binding of the four 3H-labeled ligands to the same areas [25].
• The response to BNP was reduced by 88% in chloride free Kreb's buffer, by 83% in tissues pretreated with cinanserin, an antagonist of the 5-HT2 subtype of the 5-hydroxytryptamine receptor, and by 96% in tissues pretreated with tetrodotoxin, a blocker of axonal conduction [26].

Gene context of CINANSERIN

• Classical 5-HT antagonists (methysergide, metergoline, cinanserin and methiothepin) were either without effect or facilitated the response and the 5-HT2 antagonist, ritanserin was also without effect [27].
• Selective 5-HT2 receptor antagonists devoid of alpha 1-adrenoceptor blocking properties, e.g. LY 53857 and cinanserin, fail to reduce blood pressure and sympathetic nerve activity [28].
• The DOM-induced desensitization of the 5-HT2 receptor coupled response was fully blocked by 0.1 microM cinanserin [29].

Analytical, diagnostic and therapeutic context of CINANSERIN

• Line 413 early-onset, genetically homozygous dystrophic chickens were given twice-daily intraperitoneal injections of the antiserotoninergic drug cinanserin, alone or in combination with methysergide [30].
• In the anaesthetized rat the intravenous injection of 5-HT antagonists, cinanserin and methysergide, induces in two-thirds of neurones studied, an increase in the responsiveness of dorsal horn convergent neurones to C-fibre stimulation [31].
• The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM [32].
• Iontophoresis of cinanserin did not antagonize inhibition produced by iontophoresis of 5-MeODMT or 5-HT [33].

References