Disease relevance of BMY7378

• In contrast, BMY 7378, which shows low efficacy at postsynaptic 5-HT1A receptors but high efficacy at presynaptic 5-HT1A receptors, elicited only mild hypothermia [1].
• 4. Partial agonist properties of BMY 7378 at postsynaptic sites were also indicated by doses for hypothermia being much greater than those for hyperphagia i.e., ED50 (hypothermia) greater than 2 mg kg-1, ED50 (hyperphagia) = 0.010 mg kg-1 [2].
• BMY 7378 is an agonist at 5-HT1A receptors mediating hypotension and renal sympatho-inhibition in anaesthetised cats [3].
• BMY 7378 alone decreased the incidence of motion sickness [4].
• RESULTS: In the thoracic aorta, BMY 7378 displaced noradrenaline effect to the right with pA2 values of: sham, 8.58 +/- 0.12; CHF, 8.36 +/- 0.13, and sham, 8.56 +/- 0.10; CHF, 7.99 +/- 0.13 at 4 weeks and 7 months after myocardial infarction, respectively [5].

Psychiatry related information on BMY7378

• However, 8-OHDPAT and BMY-7378 were found to increase or decrease motor activity, after injection into the median or dorsal raphe nuclei, respectively [6].

High impact information on BMY7378

• There were no effects of the 5-HT1a antagonist, BMY 7378, or the 5-HT3 antagonist, MDL 72222.(ABSTRACT TRUNCATED AT 250 WORDS)[7]
• The negative geotaxis was impaired after all 5-HT1A receptor ligands, except BMY 7378 and (+/-)-WAY 100,135 [8].
• In alpha1D fibroblasts, BMY 7378 inhibited growth and protected alpha1D-ARs from CEC alkylation while having little blocking or protecting effect on the growth induced by stimulation of fibroblasts that express alpha1A- or alpha1B-ARs [9].
• No significant changes in pHi were observed with cells treated with alpha 1D-AR antisense ODNs or the alpha 1D-AR antagonist BMY 7378 compared with untreated cells [10].
• In contrast, whereas the maximal inhibition of cortical 5-HTP accumulation by BMY 7378 (55%) was similar to that obtained with the agonists, maximal response in the hippocampus was much smaller (32%) [11].

Chemical compound and disease context of BMY7378

• The effects of three putative 5-HT1A receptor antagonists (NAN-190, BMY 7378 and WB 4101) were studied on the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) [12].

Biological context of BMY7378

• [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations [13].
• 6. Stimulation of PI hydrolysis induced by phenylephrine was not affected by BMY 7378 up to 10 nM but it was reduced significantly by BMY 7378 at higher concentrations (100 nM to 1 microM) [14].
• Further, BMY 7378 is able to phase advance circadian rhythms by approximately 1 h at night even without light exposure [15].
• Although BMY-7378 and NAN-190 both displayed high affinity for the 5-HT1A receptor (IC50 values of 0.8 and 7.5 nM, respectively), their effects, when administered alone, as well as in combination with 8-OH-DPAT, were distinct [16].
• The putative 5-HT1A receptor antagonist BMY 7378 (3-100 micrograms.kg-1 i.v.) caused reductions in blood pressure, heart rate and efferent renal nerve activity in anaesthetised cats [3].

Anatomical context of BMY7378

• In the thoracic aorta, pA(2) values in WT mice for KMD-3213 and BMY7378 were 8.25 and 8.46, respectively, and in alpha(1B)-KO mice they were 8.49 and 9.13, respectively [17].
• 4. BMY 7378 was approximately 100 fold more potent as an antagonist of phenylephrine on aortic strips (pA2 9.0 +/- 0.13) than on vas deferens (pKB 7.17 +/- 0.08) and spleen (pKB 7.16 +/- 0.21); it was ineffective on the prostate [18].
• Pharmacological evidence for alpha(1D)-adrenoceptors in the rabbit ventricular myocardium: analysis with BMY 7378 [14].
• These pharmacological findings were in fairly good agreement with findings from comparison of CRCs, with the exception of the mesenteric arteries of WT and alpha(1B)-KO mice, which showed low affinities to BMY7378 [17].
• BMY 7378 bound to membranes expressing the cloned rat alpha-1D AR with a > 100-fold higher affinity (K1 = 2 nM) than binding to either the cloned rat alpha-1A AR (Ki = 800 nM) or the hamster alpha-1B AR (Ki = 600 nM) [19].

Associations of BMY7378 with other chemical compounds

• These characteristics clearly distinguish 14 from previously-reported ligands such as the postsynaptic 5-HT1A antagonist BMY 7378 and the weak partial agonist NAN 190 which, in contrast to the compounds of this series, belong to the well-exemplified class of imido derivatives of (o-methoxyphenyl)piperazines [20].
• 4. Prazosin, 5-methylurapidil and BMY7378 acted competitively in alpha(1B)-KO carotid arteries with pA(2) of 10.3, 7.6 and 9.6, respectively [21].
• 3. BMY 7378 (8 mg kg-1, s.c.) inhibited another effect of activation of postsynaptic 5-HT1A receptors, i.e., the induction of components of the 5-HT syndrome by 8-OH-DPAT (0.5, 1.0 mg kg-1, s.c.) which suggests that BMY 7378 has antagonistic as well as agonistic effects at these sites [2].
• Conversely, the increase in perfusion pressure induced by micromolar concentrations of phenylephrine was blocked by 1 nM (+)-niguldipine, but was unaffected by BMY 7378 [22].
• In SHR aorta BMY 7378 protected alpha(1D)-adrenoceptors and in caudal arteries 5-methylurapidil protected alpha(1A)-adrenoceptors from chloroethylclonidine alkylation, allowing noradrenaline to elicit contraction [23].

Gene context of BMY7378

• The greatest increases in punished responding were produced by the buspirone analogs BMY 7378 and ipsapirone, which act at the 5-HT1A receptor [24].
• The putative selective 5-HT1A antagonists, BMY 7378 [(8-[-[4-(2-,ethoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4]- decane-7,9-dione-2-HCL] and spiperone, did not reduce MIA [25].
• In both AC01 cells and cells expressing alpha 1D-AR, BMY-7378 protected alpha 1-ARs from CEC alkylation while it had little protective effect on CEC alkylation and NA-induced IP3 production in cells expressing alpha 1B-AR [26].
• This effect was mimicked by 2 microg/side 8-OH-DPAT, a 5-HT1A agonist, but not by DOI, a 5-HT2 agonist, BMY7378, a presynaptic 5-HT1A agonist or MCPP, a 2B & 2C agonist [27].
• High concentrations of the alpha 1D-adrenoceptor antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl) 1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride), displaced bound [3H]prazosin in a single-site manner and the binding affinity was close to those for alpha 1A- and alpha 1B-adrenoceptor binding sites [28].

Analytical, diagnostic and therapeutic context of BMY7378

• The depressant effects of microiontophoretically-applied tandospirone and 5-HT, on the firing activity of CA3 pyramidal neurones in the hippocampus were blocked by the intravenous injection of the 5-HT1A receptor antagonist, BMY-7378 [29].
• In contrast to its apparent 5-HT1A antagonist properties in the behavioural experiments, BMY 7378 caused a marked and dose-dependent (0.01-1.0 mg/kg s.c.) decrease of 5-HT release in ventral hippocampus of the anaesthetized rat as detected by brain microdialysis [30].
• OBJECTIVE: To evaluate the effect of the nonselective purinergic antagonist suramin and the alpha1-adrenergic antagonists, terazosin and BMY 7378, given intravenously or infused directly into the bladder during cystometry in conscious rats with bladder outlet obstruction induced by urethral ligation [31].

References