Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake

OBJECTIVE: The analgesic effect of codeine depends on its O-demethylation to morphine via sparteine oxygenase (CYP2D6) in the liver and presumably also via this enzyme in the CNS. We studied the ability of quinidine, which is a potent inhibitor of CYP2D6, to penetrate the blood brain barrier and its possible impact on codeine O-demethylation in CNS. METHODS: The study comprised 16 extensive and one poor metaboliser of sparteine, who underwent spinal anaesthesia for urinary tract surgery or examination. Eight patients were given an oral dose of 125 mg codeine and 9 patients (including the poor metaboliser) were given 200 mg quinidine 2 h before the same dose of codeine. Plasma and spinal fluid samples were collected 2 h after codeine intake. RESULTS: Free concentrations of quinidine were 11-times lower in cerebrospinal fluid than in plasma, and ranged from 9-15 nmol.l-1. Morphine concentrations were significantly lower in patients pre-treated with quinidine, both in plasma (median 1.45 nmol.l-1, range 0.74-1.95 nmol.l-1 vs 9.86 nmol.l-1, range 4.59-28.4 nmol.l-1) and in cerebrospinal fluid (0.23, 0.16-0.61 nmol.l-1 vs 3.63, 0.6-8.09 nmol.l-1). The morphine/codeine concentration ratio in plasma (3.07 x 10 (-3), 1.68-3.68 x 10 (-3) vs 19.87 x 10 (-3), 9.87-66.22 x 10 (-3) and in cerebrospinal fluid (0.83 d 10 (-3), 0.58-1.45 x 10 (-3) vs 7.19 x 10 (-3), 2.03-17.7 x 10 (-3) was also lower. The morphine/codeine concentration ratios were significantly lower in cerebrospinal fluid both without and with quinidine, but the difference between the plasma and spinal fluid ratio was significantly smaller with quinidine than without (p = 0.0002). CONCLUSION: Quinidine penetrates the blood brain barrier poorly, but quinidine pre-treatment leads to pronounced lowering of the cerebrospinal fluid concentration of morphine after codeine intake. However, the O-demethylation of codeine in CNS may not be totally blocked by quinidine.     

The differential effect of induced muscular tension (drive) on discrimination in schizophrenics and normals.

In a discrimination task where the performance of schizophrenics and normals did not differ, an increase in muscular tension led to greater decrement in schizophrenics than in normals. The difference in decrements was interpreted as being due to the activating or energizing effects of increased drive. The results were compatible with an account utilizing a response strength ceiling, with schizophrenics considered as having greater reactivity to drive conditions or lower response strength ceilings than normals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

VERBAL ASSOCIATIVE STABILITY AND COMMONALITY AS A FUNCTION OF STRESS IN SCHIZOPHRENICS, NEUROTICS, AND NORMALS.

4 ASSOCIATIONS TO EACH OF 16 STIMULUS WORDS, 8 JUDGED TO BE ANXIETY WORDS AND 8 NEUTRAL WORDS, WERE OBTAINED UNDER RELAXED AND TIME-PRESSURE CONDITIONS FROM EACH OF 40 SCHIZOPHRENICS, 32 NEUROTICS, AND 27 NORMALS ON 2 SUCCESSIVE DAYS. SCHIZOPHRENICS AND NEUROTICS WERE SIGNIFICANTLY LESS STABLE THAN NORMALS IN THEIR ASSOCIATIONS, AND SCHIZOPHRENICS WERE SIGNIFICANTLY LESS STABLE THAN NEUROTICS IN THEIR RESPONSES TO ANXIETY WORDS. TIME PRESSURE MADE SCHIZOPHRENICS EVEN LESS STABLE AND NEUROTICS MORE STABLE. THE ASSOCIATIONS OF SCHIZOPHRENICS WERE MORE UNCOMMON THAN THOSE OF NEUROTICS OR NORMALS. ALL GROUPS GAVE MORE UNCOMMON RESPONSES WHEN RESPONDING TO ANXIETY WORDS AS COMPARED TO CONTROL WORDS. THE RESULTS SUGGEST THAT A PARTIAL DISORGANIZATION OF VERBAL HABITS IS AN ASPECT OF SCHIZOPHRENIC THOUGHT DISTURBANCE, AND THE RESULTS ARE CONSISTENT WITH A RESPONSE-STRENGTH CEILING INTERPRETATION OF THIS DISORGANIZATION. (19 REF.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduced range of sensory sensitivity in chronic nonparanoid schizophrenics.

Used a forced-choice auditory signal-detection method to test the hypothesis that, compared to acute paranoid schizophrenics, chronic nonparanoid schizophrenics would show a restricted range of sensitivity to environmental cues. 40 male chronic nonparanoid and paranoid schizophrenics served as Ss. Ability to detect the presence of an auditory cue, while concurrently tracking a visual stimulus, was measured under 2 conditions, auditory monitoring being given primary or secondary importance. In this task, a narrowed range of sensitivity implies a greater deficit in ability to detect the auditory cue when the primary focus is placed elsewhere. This deficit was significantly greater in the chronics in both initial and replication experiments. The function of restricted sensitivity in limiting the range of both relevant and distracting stimuli that are responded to by chronic nonparanoid schizophrenics is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of linguistic and cognitive skills by children with cleft palate

This study compared the early cognitive and linguistic development of young children with cleft palate (N = 28) to that of noncleft children (N = 29). Measures included the Mental scale of the Bayley Scales of Infant Development, the Minnesota Child Development Inventory, Mean Length of Utterance, and words acquired by 24 months. Children with cleft palate, although well within the normal range, performed significantly below the children in the control group on the Mental Scale of the Bayley Scales of Infant Development, some subscales of the Minnesota Child Development Inventory, and words acquired by 24 months. Differences observed in the cognitive development of children with and without cleft palate were verbal as opposed to nonverbal (i.e., linguistic in nature) and were related to hearing status at 12 months and velopharyngeal adequacy.     

Intrusion of schizophrenics' idiosyncratic associations into their conceptual performance.

Instructed 19 schizophrenic and 7 nonschizophrenic inpatients to give 10 associations which were "names of things" to each of 3 stimulus words which were category names (e.g., fruit). After approximately 2 wk. without medications, Ss performed a concept identification task which involved signaling whether or not names of specific items belonged to a given category. Names to be identified included instances of the category (e.g., apple), similar things (e.g., carrot), and dissimilar things (e.g., football). Also included were idiosyncratic associations given by S to the category word and idiosyncratic associations given by a different S. Schizophrenics produced significantly more idiosyncratic associations than nonschizophrenics on the initial association test. On the conceptual task, schizophrenics significantly more often identified their own idiosyncratic associations to the category names as instances of the category than they did for idiosyncratic associations from another patient. It is suggested that at least some idiosyncratic intrusions in the conceptual performance of schizophrenics consist of preexisting associations, as predicted by response interference theories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A factor-analytic study of religious attitudes.

"Two basic religious attitude dimensions were isolated by inverse factor analysis. The first was described as a 'Nearness of God' dimension and the other as a 'Fundamentalism-Humanitarianism' dimension. A Religious Attitude Inventory with scales designed to measure these factors was constructed and subjected to cross-validational study." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"The Differential Effect of Induced Muscular Tension (Drive) on Discrimination in Schizophrenics and Normals": Erratum.

Reports an error in the original article by William E. Broen, Jr., and Lowell H. Storms (Journal of Abnormal & Social Psychology, 1964, 68[3], 349-353). In Footnote 1 (page 349) of the article "The Differential Effect of Induced Muscular Tension (Drive) on Discrimination in Schizophrenics and Normals," the California Department of Mental Hygiene should also have been cited as supporting the study through Research Grant 61-2-20. (The following abstract of this article originally appeared in record 1964-07261-001). In a discrimination task where the performance of schizophrenics and normals did not differ, an increase in muscular tension led to greater decrement in schizophrenics than in normals. The difference in decrements was interpreted as being due to the activating or energizing effects of increased drive. The results were compatible with an account utilizing a response strength ceiling, with schizophrenics considered as having greater reactivity to drive conditions or lower response strength ceilings than normals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decreased discrimination as a function of increased drive.

In 2 samples of psychiatric patients, an increase in drive induced by gripping a hand dynamometer led to a decrease in discrimination characterized by a reduction in an appropriate response at its training stimulus. The drive also facilitated generalized dominant responses and did not increase anxiety. It was concluded that a decrease in appropriate behavior can result from an increase in a nonaversive drive. The results were in accord with a theoretical account utilizing constructs from Hull-Spence theory and including a lowered reaction potential ceiling. (21 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)