Faculty Bibliography

The effects of the two enantiomers of butaclamol and of several neuroleptics on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity was investigated. The (+) but not the (-) enantiomer of butaclamol reverses the apomorphine-elicited enzyme inhibition. (+) Butaclamol is more potent than the other tested neuroleptics. All the tested neuroleptics reverse the apomorphine-elicited enzyme inhibition but their relative potency differs. Using two criteria, namely the concentrations of neuroleptics required to reverse enzyme inhibition maximally or by 25%, the order of decreasing potency is as follows: (+) butaclamol, fluphenazine, haloperidol, pimozide, chlorpromazine. The results suggest that the reversal of apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity is a valid test model for screening antipsychotic drugs.

The effects of chlorpromazine and of some metabolites of chlorpromazine on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity were investigated. Chlorpromazine, nor1-chlorpromazine and 7-hydroxychlorpromazine reverse the apomorphine-elicited inhibition of tyrosine hydroxylase activity while nor1-chlorpromazine sulfoxide and nor2-chlorpromazine sulfoxide have no effect on this inhibition. 6-Hydroxychlorpromazine and promethazine also reverse the enzyme inhibition by apomorphine but are less potent than chlorpromazine or 7-hydroxychlorpromazine. These results show that chlorpromazine and its metabolites with antipsychotic activity are more effective in reversing the apomorphine-elicited inhibition of tyrosine hydroxylase than those metabolites which are devoid of antipsychotic activity

Endogenously depressed patients who showed an antidepressant response to the tricyclic drug imipramine continued to show sustained well being after alpha-MPT was added whereas depression returned when small doses of PCPA were added for brief periods. In one patient the antidepressant response to imipramine occurred after pre- and continued treatment with alpha-MPT. Urinary excretion levels of MHPG in one of the patients studied longitudinally did not correspond to the direction of clinical affective state but did reflect anticipated changes during alpha-MPT treatment. Implications are that serotonergic mechanisms are likely involved in the anti-depressant effects of imipramine in man

Cerebral blood flow was measured by the indicator fractionation technique in normal, acute hydrocephalic, chronic compensated hydrocephalic and craniectomized hydrocephalic cats. In the five normal cats the mean total brain blood flow was 136.1 ml/min/100 g dry weight. The six acute hydrocephalic animals demonstrated a relatively uniform 22% reduction in total blood flow. In eight chronic hydrocephalic cats CBF increased to the point where there was only an overall 7% decrease. In three hydrocephalic and craniectomized cats the CBF was reduced by 30.6%. In the acute phases there was a decrease in the number of blood vessels. Chronic compensated hydrocephalic brains had somewhat more vessels than the normal, whereas the craniectomized, massively hydrocephalic brain had a dramatic increase in both the number and caliber of blood vessels. These results clearly demonstrate that in acute obstructive hydrocephalus in cats, there is a significant decrease in CBF. The blood vessels revert to normal in shunted cats

An approach to the treatment of neonatal hydrocephalus is proposed which is intended to reduce or eliminate shunt dependency by increasing the effectiveness of remaining pathways of absorption of cerebrospinal fluid. In suitable cases, intermittent cranial compression by means of an elastic bandage or a helmet with an inflatable inner-lining may be effective. Hydrocephalus was arrested in nine of 14 children treated with this method, eight of whom have developed normally. When cranial compression is contra-indicated or not successful, the preferred method of treatment is an 'on-off' type of valve which is used intermittently to drain a fixed volume of cerebrospinal fluid. Of 18 children who had such shunts inserted, 10 have become totally independent of their shunts and their hydrocephalus has become compensated. All are of normal intelligence. Subtemporal craniectomy was performed on seven shunt-dependent children with recurrent catheter obstruction. Four have been followed for six months and three for two years and in no case has there been further malfunction of the proximal catheter