Hagan J J, Hatcher J P, Slade P D
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Eur J Pharmacol. 1995 Dec 29;294(2-3):743-51. doi: 10.1016/0014-2999(95)00627-3.
Systemic administration of 5-hydroxytryptophan (5-HTP) to guinea pigs causes species-specific, rhythmic, whole body jerks (myoclonic jerks), the frequency and amplitude of which were measured in an automated apparatus. The brain penetrant 5-HT1D receptor agonist 3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate (SKF 99101H) (3-30 mg/kg i.p.) and the selective 5-HT1A receptor agonist (+/-)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.3-3 mg/kg s.c.) dose dependently potentiated the frequency and intensity of myoclonic jerks caused by 5-HTP (100 mg/kg). Cotreatment of guinea pigs with 8-OH-DPAT (3 mg/kg s.c.) and SKF 99101H (30 mg/kg i.p.), which were inactive when given alone, gave a marked myoclonic jerk response. Conversely, the myoclonic jerk response to higher doses of 5-HTP (150 mg/kg i.p.) was dose dependently blocked by the 5-HT1D receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1 ,2,4-oxadiazol-3-yl)[1,1'-biphenyl]4-carboxamide oxalate) (ED50 0.32 mg/kg i.p.) and the selective 5-HT1A receptor antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (ED50 0.33 mg/kg i.p.). The response to 5-HTP (150 mg/kg i.p.) was also blocked by ritanserin (0.01-0.3 mg/kg i.p.). Our data therefore confirm previous reports concerning the effects of 5-HT2A/2C receptor blockade on 5-HTP induced myoclonic jerks and suggest that both 5-HT1D and 5-HT1A receptors play an important role in mediating this behavioural response.
给豚鼠全身注射5-羟色氨酸（5-HTP）会引起特定物种的、有节律的全身抽搐（肌阵挛性抽搐），其频率和幅度在自动装置中进行测量。脑渗透性5-HT1D受体激动剂3-(2-二甲基氨基乙基)-4-氯-5-丙氧基吲哚半富马酸盐（SKF 99101H）（腹腔注射3 - 30毫克/千克）和选择性5-HT1A受体激动剂(±)8-羟基-2-(二正丙基氨基)四氢萘（8-OH-DPAT）（皮下注射0.3 - 3毫克/千克）剂量依赖性地增强了由5-HTP（100毫克/千克）引起的肌阵挛性抽搐的频率和强度。单独使用无活性的8-OH-DPAT（皮下注射3毫克/千克）和SKF 99101H（腹腔注射30毫克/千克）共同处理豚鼠时，会产生明显的肌阵挛性抽搐反应。相反，5-HT1D受体拮抗剂GR 127935（N-[4-甲氧基-3-(4-甲基-1-哌嗪基)phenyl]-2'-甲基-4'-(5-甲基-1,2,4-恶二唑-3-基)[1,1'-联苯]4-甲酰胺草酸盐）（腹腔注射半数有效剂量0.32毫克/千克）和选择性5-HT1A受体拮抗剂WAY 100635（N-[2-[4-(2-甲氧基苯基)-1-哌嗪基]乙基]-N-(2-吡啶基)环己烷甲酰胺三盐酸盐）（腹腔注射半数有效剂量0.33毫克/千克）剂量依赖性地阻断了对更高剂量5-HTP（腹腔注射150毫克/千克）的肌阵挛性抽搐反应。对5-HTP（腹腔注射150毫克/千克）的反应也被利坦色林（腹腔注射0.01 - 0.3毫克/千克）阻断。因此，我们的数据证实了先前关于5-HT2A/2C受体阻断对5-HTP诱导的肌阵挛性抽搐影响的报道，并表明5-HT1D和5-HT1A受体在介导这种行为反应中都起重要作用。
