Search results for: 5HT1A, WB control
#1828767 
//
To Up
The effect of putative 5-HT1A receptor antagonists on 8-OH-DPAT-induced hypothermia in rats and mice.
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). In order to control for the alpha 1-adrenoceptor antagonist activity of NAN-190 and WB 4101, the effects of prazosin were also examined. Both NAN-190 and WB 4101 lowered body temperature in the mouse. This effect appeared to be due to their alpha 1-adrenoceptor antagonist effects as prazosin had a similar profile. Neither NAN-190, WB 4101 nor prazosin antagonised the hypothermic effects of 8-OH-DPAT. BMY 7378 slightly lowered body temperature but to a lesser extent than 8-OH-DPAT and, in contrast to the other compounds studied, also prevented a fall in body temperature on injection of 8-OH-DPAT. In the rat there was much less interference from alpha 1-adrenoceptor antagonist activity as both NAN-190 and prazosin only slightly reduced body temperature. In this species, however, NAN-190 showed marked antagonist activity against 8-OH-DPAT hypothermia. This was not due to alpha 1-adrenoceptor antagonist activity as prazosin had no effect. In the rat, as in the mouse, BMY 7378 had a partial agonist profile, whereas WB 4101 behaved essentially as an agonist. These results suggest that NAN-190 is a pure antagonist of 8-OH-DPAT-induced hypothermia in rats and that BMY 7378 and WB 4101 are, respectively, a partial agonist and an agonist in this test.(ABSTRACT TRUNCATED AT 250 WORDS)P C Moser
2805 related Products with: The effect of putative 5-HT1A receptor antagonists on 8-OH-DPAT-induced hypothermia in rats and mice.
50 ug 100ul100ug1 mg100ug100ug100ug Lyophilized1100ug Lyophilized96 wells (1 kit)100 μg
Related Pathways
#3207999 //
To Up
Centrally acting hypotensive agents with affinity for 5-HT1A binding sites inhibit forskolin-stimulated adenylate cyclase activity in calf hippocampus.
1. A number of centrally acting hypotensive agents and other ligands with high affinity for 5-hydroxytryptamine1A (5-HT1A) recognition sites have been tested on forskolin-stimulated adenylate cyclase activity in calf hippocampus, a functional model for 5-HT1A-receptors. 2. Concentration-dependent inhibition of forskolin-stimulated adenylate cyclase activity was elicited by the reference 5-HT1-receptor agonists (mean EC50 value, nM): 5-HT (22), 5-carboxamidotryptamine (5-CT, 3.2), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, 8.6), N,N-dipropyl-5-carboxamidotryptamine (DP-5-CT, 2.3), 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)-piperazine (PAPP or LY 165163, 20), 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H indole (RU 24969, 20), buspirone (65) and ipsapirone (56). Emax amounted to 18-20% inhibition for all but the latter two agonists (14%). 3. The following hypotensive agents with high affinity for 5-HT1A sites were potent agonists in this system (mean EC50 value, nM): flesinoxan (24), indorenate (99), erythro-1-(1-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethyl]-4-piperidyl )- 2-benzimidazolinone (R 28935, 2.5), urapidil (390) and 5-methyl-urapidil (3.5). The first two agents were full agonists, whereas the latter three acted as partial agonists with 60-80% efficacy. 4. Metergoline and methysergide behaved as full agonists and cyanopindolol as a partial agonist with low efficacy. Spiroxatrine and 2-(2,6-dimethoxyphenoxyethyl)aminomethyl- 1,4-benzodioxane (WB 4101) which bind to 5-HT1A sites with nanomolar affinity, were agonists and inhibited potently forskolin-stimulated adenylate cyclase in calf hippocampus, showing mean EC50 values of 23 and 15 nM, respectively. Spiroxatrine and WB 4101 yielded 90% and 50% efficacy, respectively. 5. Spiperone and methiothepin (each 1 microM) caused rightward shifts of the concentration-effect curve to 8-OH-DPAT, without loss of the maximal effect, as did the partial agonist cyanopindolol (0.1 microM) and the (-)- and (+)-enantiomers of pindolol (1 microM and 0.1 mM, respectively). 6. There was an excellent correlation (r = 0.90, P = 0.0001) between the pEC50 values (ranging from 6.4 to 8.7) of the 19 agonists tested at adenylate cyclase and their pKD for 5-HT1A recognition sites. Apparent pKB values of antagonists at adenylate cyclase and their pKD values for 5-HT1A binding sites were also significantly correlated. 7. This study further indicates that the 5-HT1A recognition site and the 5-HT receptor mediating inhibition of adenylate cyclase in hippocampus are the same. The data show that a number of centrally acting hypotensive agents with high affinity for the 5-HT1,A site are potent agonists in this model, suggesting an involvement of central 5-HTIA-receptors in the control of blood pressure.P Schoeffter, D Hoyer