Singh P P, Das P K
Psychopharmacology (Berl). 1976 Nov 10;50(2):199-204. doi: 10.1007/BF00430493.
Role of brain monoamines in the hyprothermic activity of cannabis resin (CI) in albino rats was studied using agents which influence monoamine synthesis, storage, release, reuptake, metabolism and receptor activity and monoaminergic neuronal activity. Delta-9-tetrahydrocannabinol content of resin was estimated to be 17%. Reserpine was used for comparison. CI was given orally in the dose of 50 mg/kg. Nialamide (NM) and alpha-methyl-metatyrosine (MMT) caused slight hyperthermia. p-Chlorophenylalanine (PCPA), alpha-methol-p-tyrosine (MPT), 5,6-dihydroxytryptamine (DHT, icv) and 6-hydroxydopamine (6-HD, icv) had no effect on body temperature. alpha-Methyl-dopa (m-Dopa), diethyldithiocarbamate (DDC), DDC with l-Dopa, gammabutyrolactone (GBL), phentolamine (PHENT), phenoxybenzamine (PBZ), propranolol (PROP) and imipramine (IMP) produced hypothermia. Hyprothermic activity of CI was potentiated by NM and PCPA, unaffected by DHT and m-Dopa, blocked by MMT, MPT, 6-HD, GBL, PHENT, PROP and chlorpromazine (CPZ), inhibited by DDC, DDC and l-Dopa and PBZ. CI induced hyperthermia in tolerant rats could be reversed to hypothermia by IMP. Reserpine hypothermia was blocked by NM, MPT, 6-HD and CPZ. There was a partial cross tolerance between cannabis and reserpine. Studies indicate that the hypothermic activity of CI similar to that of reserpine is mediated through central catecholamines and not 5-HT, and that noradrenaline is involved and not dopamine. However, the mechanism of action of cannabis and reserpine on noradrenergic neurone seems to be different.
利用影响单胺合成、储存、释放、再摄取、代谢和受体活性以及单胺能神经元活性的药物,研究了脑单胺在大麻树脂(CI)对白化大鼠的降温活性中的作用。树脂中δ-9-四氢大麻酚含量估计为17%。利血平用于比较。CI以50mg/kg的剂量口服。尼亚酰胺(NM)和α-甲基间酪氨酸(MMT)引起轻微体温升高。对氯苯丙氨酸(PCPA)、α-甲基对酪氨酸(MPT)、5,6-二羟基色胺(DHT,脑室内注射)和6-羟基多巴胺(6-HD,脑室内注射)对体温无影响。α-甲基多巴(m-Dopa)、二乙基二硫代氨基甲酸盐(DDC)、DDC与左旋多巴、γ-丁内酯(GBL)、酚妥拉明(PHENT)、酚苄明(PBZ)、普萘洛尔(PROP)和丙咪嗪(IMP)产生体温过低。CI的降温活性被NM和PCPA增强,不受DHT和m-Dopa影响,被MMT、MPT、6-HD、GBL、PHENT、PROP和氯丙嗪(CPZ)阻断,被DDC、DDC和左旋多巴以及PBZ抑制。CI诱导的耐受大鼠体温过高可被IMP逆转至体温过低。利血平引起的体温过低被NM、MPT、6-HD和CPZ阻断。大麻和利血平之间存在部分交叉耐受性。研究表明,CI与利血平相似的降温活性是通过中枢儿茶酚胺介导的,而非5-羟色胺,且涉及去甲肾上腺素而非多巴胺。然而,大麻和利血平对去甲肾上腺素能神经元的作用机制似乎不同。