Evaluation of xanthotoxol for central nervous system activity.

Xanthotoxol (XT), 8-hydroxypsoralen, exhibited dose-graded sedative activity in dogs, cats, rats, mice and hamsters. At doses of 5-20 mg/kg intraperitoneally (i.p.) in cats and 3-100 mg/kg orally (p.o.) in dogs, XT blocked predatory mouse/rat killing behavior. In mice, XT (10-300 mg/kg i.p.) exhibited a dose-dependent reduction in locomotor activity but was less potent in this regard than reference diazepam (10-100 mg/kg i.p.). XT in mice (0.1-10.0 mg/kg i.p.) and in hamsters (0.1-10.0 mg/kg p.o.) antagonized amphetamine-induced hypermobility but was less potent than diazepam. XT elevated the electrical threshold in foot-shock-induced fighting behavior in rats. XT (0.1-30.0 mg/kg p.o.) potentiated pentobarbital-induced narcosis in hamsters at otherwise subeffective doses of pentobarbital. Conditioned avoidance responses in rats were not significantly altered with 1-3 mg/kg i.p. and 30-100 mg/kg p.o. doses of XT but 300 mg/kg p.o. blocked both conditioned and unconditioned response. Doses of 100-1000 mg/kg i.p. of XT in mice were used to study 48-h acute toxicity of XT and its LD50 was estimated to be 468 mg/kg. Doses of 10, 40 and 80 mg/kg p.o. were used to study the chronic toxicity of XT in rats for 6 months and no side effects or abnormalities in reproductive activity or endocrine integrity were noted. The F1 generation of rats from 6-month XT-treated parents were free of teratogenic effects.

Action of some amides of substituted ethylenediamines on central nervous system.

Five of the substituted ethylenediamine amides (LMG I to V) were tested for various CNS attributes and for acute toxicity (24 hr mortality). All compounds were potent analgesics in various animal tests, LMG V being most potent. All reduced spontaneous activity of mice and potentiated ether anaesthesia. However, CAR was not altered and anti-MES were not pronounced in rats. Compounds appear to have a wide safety margin considering ED50 and LD50 in mice.

Pharmacological studies of certain amides of substituted ethylenediamines - I.

Five substituted amides of ethylenediamines produced hypotension in dogs, which was not blocked by atropine, mepyramine and propranolol. The amides potentiated the pressor responses to Adr and NA and antagonised the depressor responses to Ach and histamine. The compounds also antagonised Ach-induced contractions on the frog rectus abdominis muscle and of carbachol on rat isolated colon suggesting d-tc and atropine-like actions respectively. Antihistaminic activity was observed on guinea pig isolated ileum as on dog blood pressure. Adr and NA-induced relaxation of rabbit isolated jejunum was potentiated. Finally Adr and NA-induced contractions of rat isolated seminal vesicle was antagonised.

Sedative action of some substituted benzylamides.

Substituted benzylamide derivatives of amino acylamide (compound A,B,C, & D) were found to be less potent local anaesthetics than lignocaine and procaine. However, the four compounds exhibited sedation without ptosis and reduced spontaneous locomotor activity better than methaqualone. Compound A alone antagonised methylamphetamine induced hypermotor activity. The test compounds potentiated hexobarbitone induced hypnosis. Three compounds antagonised calcium induced stoppage of isolated heart of frog. Except compound C all caused a transitory fall of blood pressure in dog which was not blocked either by atropine or propranolol. These compounds showed neuromuscular blockade and possessed slight analgesic activity but were devoid of anticonvulsant and tranquillizing activity. LD 50 values were calculated to be 164.1 +/- 23.0, 229.1 +/- 51.0, 181.6 +/- 28.18 and 416+/-38.2 mg/kg for compounds A,B,C & D respectively.