Effects of monoamine oxidase inhibitors and amphetamine on hypothermia produced by halothane

Abstract

Summary1. In cats, the effects of tranylcypromine and pheniprazine, two monoamine oxidase (MAO) inhibitors with strong amphetamine-like actions, of pargyline, an inhibitor without amphetamine-like actions, and of amphetamine itself, were examined on the hypothermia produced by a 2 hr period of halothane inhalation. 2. The hypothermia was prevented by intraperitoneal injections of the three MAO inhibitors. Tranylcypromine and pheniprazine acted in doses of a few milligrams, pargyline in doses of over 100 mg. 3. The hypothermia was prevented by injections into the cerebral ventricles of tranylcypromine and pheniprazine, in doses which were effective also on intraperitoneal injection; intraperitoneal injections were sometimes more effective. The large doses of pargyline needed to prevent the hypothermia when injected intraperitoneally were not tested by the intraventricular route, as the injections had to be made in a volume of 01 ml. In smaller doses intraventricular pargyline was not effective. 4. The hypothermia was prevented by an intraperitoneal or intraventricular injection of amphetamine in a dose as little as 1 mg; intraperitoneal injections were sometimes more effective. 5. The effects of tranylcypromine and pargyline given intraperitoneally, and of amphetamine given intraventricularly as well, were also examined on the hypothermia produced by an intraventricular injection of 200 ,g noradrenaline. The two MAO inhibitors and amphetamine prevented the hypothermia, or greatly reduced it. 6. It is concluded (a) that even on intraventricular injection the MAO inhibitors must first be absorbed into the blood stream before they can prevent the hypothermia of a halothane anaesthesia; (b) that their action may not be solely on the anterior hypothalamus ; and (c) that they may not act only through MAO inhibition.

Hypothermia produced in mice by histamine acting on the central nervous system

“…In this connexion, the ability of histamine to stimulate the adrenal medulla (Burn & Dale, 1926) is well authenticated. In addition amphetamine prevents the development of the hypothermia produced by intraventricular injections of noradrenaline both in mice (Brittain, 1966) and in cats (Feldberg & Lang, 1970). Tranylcypromine antagonizes the hypothermia produced by intraventricular injections of noradrenaline in cats, and incidentally, not only antagonizes the hypothermia produced by halothane anaesthesia but also reverses the response to produce an increase in temperature (Feldberg & Lang, 1970).…”

“…Tranylcypromine antagonizes the hypothermia produced by intraventricular injections of noradrenaline in cats, and incidentally, not only antagonizes the hypothermia produced by halothane anaesthesia but also reverses the response to produce an increase in temperature (Feldberg & Lang, 1970). Feldberg & Lang (1970) discuss many possible mechanisms concerning the mode of action of monoamine oxidase inhibitors and amphetamine in preventing the hypothermia produced by noradrenaline and halothane. They point out that tranylcypromine has amphetamine-like actions and that it may act by virtue of these rather than by inhibition of monoamine oxidase.…”

“…In addition amphetamine prevents the development of the hypothermia produced by intraventricular injections of noradrenaline both in mice (Brittain, 1966) and in cats (Feldberg & Lang, 1970). Tranylcypromine antagonizes the hypothermia produced by intraventricular injections of noradrenaline in cats, and incidentally, not only antagonizes the hypothermia produced by halothane anaesthesia but also reverses the response to produce an increase in temperature (Feldberg & Lang, 1970). Feldberg & Lang (1970) discuss many possible mechanisms concerning the mode of action of monoamine oxidase inhibitors and amphetamine in preventing the hypothermia produced by noradrenaline and halothane.…”

Metyrapone blunts stress-induced hyperthermia and increased locomotor activity independently of glucocorticoids and neurosteroids

“…It may therefore enhance noradrenaline and dopamine neurotransmission. However, COMT and MAO inhibitors are known to rather trigger hyperthermia and enhanced motor activity (Feldberg and Lang, 1970;Ashkenazi et al, 1983;Rivas et al, 1999). Metyrapone can also modify serotonin neurotransmission by upregulating serotonin 5-HT 1A receptor through its effect on intracellular level of corticosteroid (Lopez et al, 1998).…”