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Indirect sympathomimetic agents and cerebral blood flow and metabolism.

The effects upon cerebral blood flow (CBF) and oxygen consumption (CMRO2) of the infusion into the internal carotid artery of tyramine and amphetamine were investigated in 24 anaesthetized baboons. The infusion of tyramine was without effect upon CBF and CMRO2 at normocapnia, even at concentrations which significantly raised arterial blood pressure. However, marked reductions in cerebral blood flow were noted at hypercapnia during the infusion of tyramine (2.5 X 10(-7) moles/kg/min). The infusion of amphetamine (7.5 X 10(-10) moles/kg/min) resulted in significant increases in CBF (32%) and CMRO2 (37%). However, an increased concentration of amphetamine (2.5 X 10(-7) moles/kg/min) significantly reduced CBF (22%) and CMRO2 (20%). It is suggested that amphetamine, by virtue of being able to cross the blood--brain barrier and interact with the cerebral monoamine systems, is able to influence cerebral blood flow by inducing changes in cerebral metabolism, and that the minimal reactivity of the cerebral circulation to the infusion of tyramine is the result of the inability of tyramine to cross the blood--brain barrier.

Animals↗

Intestinal obstruction following previous myomectomy and the use of beta-sympathomimetics in pregnancy.

Two cases of intestinal obstruction in pregnancy following previous myomectomy are reported. The use of tocolytic agents to suppress premature uterine contractions may be a predisposing factor and probably intensifies the obstruction. As the symptoms mimic the normal side-effects of pregnancy, the diagnosis is often delayed. Laparotomy was done, as initial conservative treatment was unsuccessful in both instances. A live baby was delivered in the first case, whilst the second case ended in an abortion.

Adrenergic beta-Agonists↗

Central and peripheral cholinesterase inhibition: effects on anterior pituitary and sympathomimetic function.

Ten physically healthy inpatients of mixed diagnosis received, in a randomized, counterbalanced double-blind paradigm, physostigmine (22 micrograms/kg) and neostigmine (11 micrograms/kg). Infusions were separated by at least 2 days. The differential effects of physostigmine and neostigmine on plasma concentrations of cortisol, prolactin, growth hormone, ACTH, beta-endorphin/beta-lipotropin-like immunoreactivity, dopamine, norepinephrine, and epinephrine are reported. Administration of physostigmine, unlike that of neostigmine, was associated with statistically significant increases in plasma concentrations of cortisol, prolactin, ACTH, beta-endorphin/beta-lipotropin-like immunoreactivity, and epinephrine, presumably via central mechanisms. In a separate study, 15 subjects, mostly depressed inpatients, were pretreated with methscopolamine (0.75 mg) on one day and scopolamine (0.5 mg) on another day, at least 2 days apart, in a randomized, counterbalanced double blind paradigm and subsequently on each day received physostigmine (22 micrograms/kg). Scopolamine significantly attenuated the physostigmine-associated increase in plasma concentrations of cortisol, growth hormone, prolactin, ACTH, and dopamine compared to methscopolamine, and a close-to-significant attenuation of epinephrine as well. These results provide further evidence that physostigmine's effects on plasma concentrations of pituitary hormones and epinephrine occur via central mechanisms and are muscarinically mediated.

Adrenocorticotropic Hormone↗

Potentiating actions of tranylcypromine and moclobemide on the sympathomimetic activity of dopamine.

Ex vivo investigations were carried out to study the potentiating actions of the MAOIs moclobemide and tranylcypromine on peripheral alpha- and beta-adrenergic effects of dopamine. Isolated rat vas deferens and atria were used. Preliminary experiments showed that both moclobemide and tranylcypromine did not affect the response to noradrenaline, while they enhanced the response to tyramine. By comparison of the responses to dopamine in control and reserpinized rats, it was shown that dopamine acts in a direct and indirect manner on both the tissues tested. Two concentrations (20, 40 mg/kg, i.p.) of moclobemide were tested and administered at different time periods (2, 5 or 24 h) before the animals were sacrificed. Two concentrations (2, 20 mg/kg, i.p.) of tranylcypromine were tested at different intervals of time (2, 24 h). The results obtained pointed out that: (1) Moclobemide 20 mg/kg potentiated the alpha-adrenergic response to dopamine only 2 h after administration while 40 mg/kg exerted a potentiation which was evident not only 2 but also 5 h after administration. Both doses were ineffective 24 h after administration. (2) Moclobemide 20 and 40 mg/kg potentiated the beta-adrenergic response to dopamine. The effect was present 2 and 5 h after administration but it was absent 24 h after. (3) Tranylcypromine 20 mg/kg potentiated the alpha-adrenergic response to dopamine: this effect was present after 2 h from pretreatment and was still evident after 24 h. The lower concentration of tranylcypromine (2 mg/kg) enhanced the response to dopamine only after 24 h from pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗