BMY 7378 dihydrochloride

• CAT Number: I010354
• CAS Number: 21102-95-4
• Molecular Formula: C22H33Cl2N3O3
• Molecular Weight: 458.424
• Purity: ≥95%
• Synonyms: 8-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride
• Target: Neuronal Signaling
• Solubility: Soluble to 100 mM in water
• Storage: Store at RT
• IUPAC Name: 8-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione;dihydrochloride
• InChI: InChI=1S/C22H31N3O3.2ClH/c1-28-19-7-3-2-6-18(19)24-13-10-23(11-14-24)12-15-25-20(26)16-22(17-21(25)27)8-4-5-9-22;;/h2-3,6-7H,4-5,8-17H2,1H3;2*1H
• InChIKey: NIBOMXUDFLRHRV-UHFFFAOYSA-N
• SMILES: COC1=CC=CC=C1N2CCN(CC2)CCN3C(=O)CC4(CCCC4)CC3=O.Cl.Cl

BMY 7378 is an agonist at 5-HT1A receptors mediating hypotension and renal sympatho-inhibition in anaesthetised cats. BMY 7378 is also an alpha (2C)-adrenoceptor antagonist. BMY 7378 is a hypotensive agent in the rat, but that its actions are mediated, in part, by central 5-HT(1A) receptor stimulation in the adult and by a nonserotonergic mechanism in the young rat.

Reference

1. Eur J Pharmacol. 1990 Feb 13;176(3):331-40.
Further investigation of the in vivo pharmacological properties of the putative
5-HT1A antagonist, BMY 7378.
Sharp T(1), Backus LI, Hjorth S, Bramwell SR, Grahame-Smith DG.
Author information:
(1)MRC, Radcliffe Infirmary, Oxford, U.K.
The present study examined the actions of the putative 5-HT1A antagonist BMY 7378
on central pre- and postsynaptic 5-HT1A function in the rat in vivo. Unlike the
direct acting 5-HT1A agonist 8-hydroxy-2-(di-n-pro-pylamino)tetralin (8-OH-DPAT),
BMY 7378 (0.25-5 mg/kg s.c.) did not induce the full postsynaptically mediated
5-HT behavioural syndrome (forepaw treading, head weaving, flat body posture
hindlimb abduction). Indeed, the maximal 5-HT behavioural syndrome scores of BMY
7378 were about 10% of those for 8-OH-DPAT. Following pretreatment, however, BMY
7378 dose dependently (0.25-5 mg/kg s.c.) reduced to undetectable levels forepaw
treading and head weaving induced by 8-OH-DPAT (0.75 mg/kg s.c.). BMY 7378 also
inhibited stereotypy and locomotor activity induced by 0.5 mg/kg apomorphine
although this effect was only statistically significant at the highest dose
tested (5 mg/kg). 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. This effect of BMY 7378 had a similar
onset and duration of action but with slightly reduced efficacy compared to that
previously described for 8-OH-DPAT. As with 8-OH-DPAT, the inhibitory effect of
BMY 7378 on 5-HT release was attenuated by pretreatment with the 5-HT1
receptor/beta-adrenoceptor antagonist pindolol (8 mg/kg s.c.) but not its
counterpart propranolol (20 mg/kg s.c.). Pretreatment with a combination of the
beta 1- and beta 2-adrenoceptor antagonists metoprolol (4 mg/kg s.c.) and ICI 118
551 (4 mg/kg s.c.), respectively, did not alter the 5-HT response to BMY 7378.
From these data we conclude that BMY 7378 is a mixed agonist/antagonist at
central 5-HT1A receptors.
2. Eur J Pharmacol. 1987 Jun 4;137(2-3):293-4.
BMY 7378, a buspirone analog with high affinity, selectivity and low intrinsic
activity at the 5-HT1A receptor in rat and guinea pig hippocampal membranes.