title: Evidence for a 5-HT1D receptor-mediated hypothermic effect of the alpha 1-adrenoceptor agonist, SDZ NVI-085, in guinea-pigs.
abstract: The alpha 1-adrenoceptor agonist, SDZ NVI-085 ((-)-(4aR,10aR)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4- methyl-9-(methylthio)-2H-naphth[2,3-b]-1,4-oxazine.HCl; 1 mg/kg i.p.), decreased body temperature of guinea-pigs. Two 5-HT1D receptor antagonists, GR127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl- 1,2,4-oxadiazol-3yl)[1,1-biphenyl]-4-carboxamide) and PAPP (p-aminophenylethyl-m-trifluoromethylphenyl piperazine; both compounds at 1 mg/kg i.p., -30 min) blocked this response, whilst the alpha 1-adrenoceptor blocker prazosin (1 mg/kg i.p.) and the 5-HT1A receptor antagonist, SDZ 216-525 (methyl 4-(-[4-(1,1m3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyl ]-1-piperazinyl)1H- indole-2-carboxylate; 1 mg/kg i.p.) were inactive. Another alpha 1-adrenoceptor agonist, St 587 (2-(2-chloro-5-trifluoromethylphenylimino)-imidazoline; 1 mg/kg i.p.) did not alter body temperature. SDZ NVI-085-induced hypothermia in guinea-pigs is probably mediated by 5-HT1D receptors.
authors.affiliation: Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
authors.forename: H O
authors.initials: HO
authors.lastname: Kalkman
authors.forename: V
authors.initials: V
authors.lastname: Neumann
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001952:Bridged-Ring Compounds; D010069:Oxadiazoles; D010078:Oxazines; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C074349:SDZ NVI-085; C030655:St 587; C090701:GR 127935; C044643:LY 165163; D003000:Clonidine; D011224:Prazosin