Noscapine was administered to five healthy volunteers in a randomized crossover design, as an intravenous infusion of 66 mg, and as an oral 150 mg dose of either rapidly dissolving tablets or a tablet containing ion exchange resin-bound noscapine. After i.v. administration, the disposition of noscapine was bi-exponential with an elimination half-life of 2.6 h; the total plasma clearance was 22 ml/min/kg and the volume of distribution (Vdarea) was 4.7 l/kg. The absolute oral bioavailability was 30%, with a 3.6-fold interindividual variation. There was no pharmacokinetic evidence to support a prolonged action of the ion exchange resin tablet.

No abstract

The antinociceptive effects of the stable adenosine analogues N6-phenylisopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamidoadenosine (NECA) were investigated in conscious rats using cutaneous thermal tests (hot plate and tail flick). Subcutaneous administration of the adenosine analogues induced a dose-dependent antinociceptive response for all agents. However, NECA was approximately 15 times more potent than PIA and CHA. Approximately the same potency order and response was seen when the adenosine analogues were administered intrathecally at the lumbar level. By this route of administration, the adenosine analogues were approximately 10-20 times more potent than after S.C. administration. Intracerebroventricular administration (lateral ventricles), however, induced a variable response, in most cases a slight hyperalgesia. The nonspecific adenosine antagonist theophylline (S.C.) rapidly reduced the antinociceptive effect induced by PIA (S.C.) but enprofylline, a bronchodilating xanthine with low ability to antagonize adenosine did not influence PIA-induced antinociception. It is concluded that stable adenosine analogues and presumably adenosine itself have potent antinociceptive effects via specific adenosine receptors in the rat. The effects seem to be mediated mainly by a spinal mechanism of action.

No abstract

Adrenaline is the drug of choice for management of the anaphylactic reaction. The objective of this study was to compare systemic absorption of adrenaline after administration by different routes to healthy volunteers. Ten puffs (1.5 mg as adrenaline base) with 10-15 s intervals between them followed 2 h later by 20 puffs (3 mg) of adrenaline from a pressurized aerosol (Medihaler-Epi, 3M Riker, 14.0 mg/ml adrenaline acid tartrate) were sprayed into the cheek pouch or inhaled through the mouth or the nostrils. Adrenaline was also administered to the eyes by giving 2 drops (1 mg) of Isopto-Epinal (Alcon, 10 mg X ml-1). Finally, 0.5 ml (0.5 mg) of adrenaline was given subcutaneously in the upper arm of the same individuals. The systemic absorption was determined by measuring plasma adrenaline levels and effects on blood pressure, heart rate and finger tremor before and 5, 15, 30, 60, 90, and 120 min after adrenaline administration. Adrenaline given as eye-drops did not have any significant effect on these parameters. Subcutaneously administered adrenaline caused within 5 min a significant increase of plasma adrenaline level (from 1.0 +/- 0.2 to peak of 6.5 +/- 1.2 nM) which gradually decreased during 2 h. This mode of adrenaline administration increased the systolic blood pressure by a maximum of 11 +/- 3.5 mmHg, heart rate by 9 +/- 2.2 beats X min-1, tremor ratio by 4 +/- 0.6 and reduced the diastolic blood pressure by 18 +/- 4.7 mmHg. The cardiovascular effects were approximately maximum 15 min after administration and lasted almost 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)