morphinans and Amnesia

(1) Dimemorfan, an antitussive for more than 25 years, has previously been reported to be a relative high-affinity ligand at sigma-1 (sigma(1)) receptor with the K(i) value of 151 nM. (2) To test whether dimemorfan has anti-amnesic effects similar to a sigma(1) receptor agonist, this study examined its effects on scopolamine- and beta-amyloid peptide-(25-35)-induced amnesia in mice. (3) Dimemorfan (10-40 mg kg(-1), i.p.) administered 30 min before the training trial, immediately after the training trial, or 30 min before the retention test significantly improved scopolamine (1 mg kg(-1), i.p.)- or beta-amyloid peptide-(25-35) (3 nmol mouse(-1), i.c.v.)-induced amnesia in a step-through passive avoidance test. Dimemorfan (5-40 mg kg(-1), i.p.) pretreatment also attenuated scopolamine (8 mg kg(-1), i.p.)-induced amnesia in a water-maze test. And, these anti-amnesic effects of dimemorfan, like the putative sigma(1) receptor agonist (+)-N-allylnormetazocine ((+)-SKF-10047), were antagonized by a sigma receptor antagonist haloperidol (0.25 mg kg(-1), i.p.). (4) These results indicated that dimemorfan has anti-amnesic effects and acts like a sigma(1) receptor agonist.

Topics: Amnesia; Amyloid beta-Peptides; Animals; Avoidance Learning; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred ICR; Morphinans; Peptide Fragments; Phenazocine; Receptors, sigma; Scopolamine

The cardiovascular effects of high doses of butorphanol (0.3-0.45 mg . kg-1) plus 60 per cent N2O anaesthesia were measured at unconsciousness, following tracheal intubation, and immediately before and at one and ten minutes after surgical stimulation in 17 A.S.A. class I and II patients undergoing elective gastric or gall bladder surgery. Butorphanol and N2O produced unconsciousness with only small decreases in heart rate and cardiac output but did not result in sufficient analgesia to block or treat stimulation of the cardiovascular system secondary to tracheal intubation or surgical incision, even when supplemented with additional butorphanol to high cumulative dose levels (1.0 mg . kg-1). The data suggest that even high dose butorphanol - N2O anaesthesia requires supplementation with other anaesthetics or anaesthetic adjuvants to prevent cardiovascular stimulation during general abdominal surgery.

Topics: Adjuvants, Anesthesia; Amnesia; Analgesia; Anesthesia, General; Blood Pressure; Butorphanol; Cardiac Output; Cardiovascular System; Heart Rate; Humans; Intraoperative Period; Morphinans; Nitrous Oxide; Stroke Volume; Vascular Resistance