- Email: [email protected]
NO EFFECTS OF QUATERNARY NEUROLEPTICS ON HUMAN PROLACTIN AND ADENYLCYCLASE
493
categories (vasogenic, cytotoxic, and interstitial). Cytotoxic oedema is due to hypoxia, and seems to characterise the cedema found in 1 mildly retarded case. This patient involves three
(male, age fifteen years at
at
death) had hemiplegia and
"anoxia
birth"; cerebellar cell loss and demyelination, and cerebral
cortical neuronophagia with eosinophilia were reported. Brain herniation is most likely to occur with vasogenic cedema, which is related to brain tumour, infarction, contusion, lead encephalopathy, and purulent meningitis.7 Among the mildly retarded, no tumours were reported; meningeal changes suggestive of meningitis were reported in 1 case, but there was no oedema. Infarction may have been involved in 1 case (male, age thirteen years); in the clinical history, the encephalopathy was attributed to postnatal vascular occlusion. The probable cause
vasogenic oedema could not be determined in most mildly retarded (or other) cases. It is not known whether the œdema was causally related to retardation or occurred in persons already retarded. Oedema could have occurred, for example, as a result of head injuries in retarded persons with epilepsy ; clinical records of 5 of the 10 mildly retarded with cedema, but only 2 of the 6 with herniations, mentioned epilepsy.
We believe that the
potential advantages of the quaternary high enough to warrant further investigations, aimed at clarifying their pharmacological effects compared with those of the tertiary analogues. neuroleptics
are
Parliament
of the
Further studies on oedema in the retarded may be warranted; detailed clinical histories, including electroencephalographic findings, would be needed. more
This work
was
supported
in part
by a grant from
the University of assistant professor in of Waterloo.
Waterloo, Ontario, Canada, received while I the Department of Kinesiology,
University
was
Birth Defects Institute,
State Department of Health, Albany, N.Y., U.S.A.
GERHARD LANGER HO SAM AHN JAMES M. PEREL MAYNARD H. MAKMAN EDWARD J. SACHAR
Department of Psychiatry, University College of Physicians and Surgeons New York, N.Y. 10032, U.S.A., and Department of Biochemistry and Pharmacology, A. Einstein College of Medicine, Bronx, N.Y. Columbia
New Dental and
Optical Charges Details were given in answer to a written question in the House of Commons on Feb. 17 of the increased charges for dental and optical treatment which the Chancellor of the Exchequer announced in July as part of the savings in public expenditure. Mr DAVID ENNALS, Secretary of State for Social Services, said that the charge for most courses of dental treatment would be increased from 3-50 to 5; this was a maximum charge, and patients who required only a small amount of treatment would pay less than this. The charges for the supply of dentures (present maximum, £ 12) would be: Synthetic resin
ANTHONY P. POLEDNAK*
dentures *Present address:
Radiological and Environmental Research Division, Argonne Illinois 60439, U.S.A.
National Laboratory, Argonne,
Bearing 1, 2, or 3 teeth Bearing 4-8 teeth Bearing more than 8 teeth Maximum for
more
than
one
Perphenazine-N-dimethyldichloride, prochlorperazine-Ndimethyldichloride, and haloperidol-N-methylchloride were synthesised by the method of Huang et al.4 Authenticity was proved by elemental analysis, and purity was established by spectroscopic techniques. The method for the adenylcyclase assay has been described previously.’ Although intravenous injections of perphenazine 0.5mg and prochlorperazine 2. 0 mg resulted in prompt release of prolactin in five male volunteers, injections of equimolar doses of the quaternary ammonium salts of these drugs did not release human prolactin. Also in contrast to their tertiary analogues, the quaternary neuroleptics did not block dopamine-sensitive adenylcylase activity in striatal homogenates of the cebus monkey. 1
Fog, R. L., Randrup, A., Pakkenberg,
H.
Psychopharmacologia, 1968, 12,
428. 2. Kebabian,
J. W., Petzold, G. W., Greengard, P. Proc. nat. Acad. Sci. U.S.A. 1972, 69, 2145. 3 Kleinberg, D. L., Noel, G. L., Frantz, A. G.J. clin. Endocr. Metab. 1971, 33, 873. 4. Huang, C. L., Mir, G. M., Yeh, J. Z. J. pharm. Sci. 1970, 59, 976. 5 Ahn, H. S., Mishra, R. K., Demirjan, C., Makman, M. H. Brain Res. 1976, 116, 437.
/;
/:
10 11 12
15 16 17
20
30
den-
ture
NO EFFECTS OF QUATERNARY NEUROLEPTICS ON HUMAN PROLACTIN AND ADENYLCYCLASE SIR,—Quaternary ammonium salts of neuroleptic drugs cannot penetrate the blood/brain barrier in significant amounts. Thus they could be valuable tools for evaluating possible psychotropic effects of neuroleptics which might be triggered by the action of the drugs on structures outside the blood/brain barrier. Quaternary neuroleptics are roughly equipotent to their tertiary, conventional counterparts in behavioural tests in rats after microinjections into the central nervous system.’ Conventional tertiary neuroleptics inhibit dopamine-sensitive adenylcyclase activity2 and release prolactin in man,3 but are their quaternary counterparts equally effective?
Metal dentures and bridges
The charges for crowns, inlays, pinlays, and gold fillings would be £10 for each tooth restored, with a maximum of C30 if more than 3 teeth were restored; there would also be a maximum of C30 for a combination of any of these items of treatment. The special charges for particular high-cost items of treatment, such as crowns (which figured in about 3% of courses of treatment) had been introduced with reluctance, but this was the only way to keep the ordinary maximum charge down to a level which would not deter people from seeking
regular treatment. Optical charges would be raised from 2-25 to 2 90 for each single-vision lens, from 4-25 to £5.50 for each fused glass bifocal lens, and from ,5 to 6-15 for any other type of lens (including solid glass or plastic bifocals). Regulations implementing these proposals would be laid before Parliament to come into effect on April 1; the last increases in dental and optical charges came into effect on Jan. 1,1976. -
Blood for Private Patients
In answer to questions from Mr LAURIE PAVITT in the House of Commons on Feb. 8 concerning the use by private patients of blood collected by the National Blood Transfusion Service Mr ROLAND MOYLE, Minister of State, Department of Health and Social Security, said that no separate financial or administrative arrangements applied to blood used by private patients in N.H.S. hospitals. Daily charges were inclusive of accommodation and all services. Where blood was supplied to a private hospital or nursing home, no charge was made for the blood itself, but if circumstances justified, a charge might be made for the pathological and other services involved. Senior officials of the National Blood Transfusion Service were employees of the N.H.S. authorities. No instructions issued by the Department of Health barred them from serving on the board of directors of a private hospital or of organisations pro-
viding private-patient hospital cover.
categories (vasogenic, cytotoxic, and interstitial). Cytotoxic oedema is due to hypoxia, and seems to characterise the cedema found in 1 mildly retarded case. This patient involves three
(male, age fifteen years at
at
death) had hemiplegia and
"anoxia
birth"; cerebellar cell loss and demyelination, and cerebral
cortical neuronophagia with eosinophilia were reported. Brain herniation is most likely to occur with vasogenic cedema, which is related to brain tumour, infarction, contusion, lead encephalopathy, and purulent meningitis.7 Among the mildly retarded, no tumours were reported; meningeal changes suggestive of meningitis were reported in 1 case, but there was no oedema. Infarction may have been involved in 1 case (male, age thirteen years); in the clinical history, the encephalopathy was attributed to postnatal vascular occlusion. The probable cause
vasogenic oedema could not be determined in most mildly retarded (or other) cases. It is not known whether the œdema was causally related to retardation or occurred in persons already retarded. Oedema could have occurred, for example, as a result of head injuries in retarded persons with epilepsy ; clinical records of 5 of the 10 mildly retarded with cedema, but only 2 of the 6 with herniations, mentioned epilepsy.
We believe that the
potential advantages of the quaternary high enough to warrant further investigations, aimed at clarifying their pharmacological effects compared with those of the tertiary analogues. neuroleptics
are
Parliament
of the
Further studies on oedema in the retarded may be warranted; detailed clinical histories, including electroencephalographic findings, would be needed. more
This work
was
supported
in part
by a grant from
the University of assistant professor in of Waterloo.
Waterloo, Ontario, Canada, received while I the Department of Kinesiology,
University
was
Birth Defects Institute,
State Department of Health, Albany, N.Y., U.S.A.
GERHARD LANGER HO SAM AHN JAMES M. PEREL MAYNARD H. MAKMAN EDWARD J. SACHAR
Department of Psychiatry, University College of Physicians and Surgeons New York, N.Y. 10032, U.S.A., and Department of Biochemistry and Pharmacology, A. Einstein College of Medicine, Bronx, N.Y. Columbia
New Dental and
Optical Charges Details were given in answer to a written question in the House of Commons on Feb. 17 of the increased charges for dental and optical treatment which the Chancellor of the Exchequer announced in July as part of the savings in public expenditure. Mr DAVID ENNALS, Secretary of State for Social Services, said that the charge for most courses of dental treatment would be increased from 3-50 to 5; this was a maximum charge, and patients who required only a small amount of treatment would pay less than this. The charges for the supply of dentures (present maximum, £ 12) would be: Synthetic resin
ANTHONY P. POLEDNAK*
dentures *Present address:
Radiological and Environmental Research Division, Argonne Illinois 60439, U.S.A.
National Laboratory, Argonne,
Bearing 1, 2, or 3 teeth Bearing 4-8 teeth Bearing more than 8 teeth Maximum for
more
than
one
Perphenazine-N-dimethyldichloride, prochlorperazine-Ndimethyldichloride, and haloperidol-N-methylchloride were synthesised by the method of Huang et al.4 Authenticity was proved by elemental analysis, and purity was established by spectroscopic techniques. The method for the adenylcyclase assay has been described previously.’ Although intravenous injections of perphenazine 0.5mg and prochlorperazine 2. 0 mg resulted in prompt release of prolactin in five male volunteers, injections of equimolar doses of the quaternary ammonium salts of these drugs did not release human prolactin. Also in contrast to their tertiary analogues, the quaternary neuroleptics did not block dopamine-sensitive adenylcylase activity in striatal homogenates of the cebus monkey. 1
Fog, R. L., Randrup, A., Pakkenberg,
H.
Psychopharmacologia, 1968, 12,
428. 2. Kebabian,
J. W., Petzold, G. W., Greengard, P. Proc. nat. Acad. Sci. U.S.A. 1972, 69, 2145. 3 Kleinberg, D. L., Noel, G. L., Frantz, A. G.J. clin. Endocr. Metab. 1971, 33, 873. 4. Huang, C. L., Mir, G. M., Yeh, J. Z. J. pharm. Sci. 1970, 59, 976. 5 Ahn, H. S., Mishra, R. K., Demirjan, C., Makman, M. H. Brain Res. 1976, 116, 437.
/;
/:
10 11 12
15 16 17
20
30
den-
ture
NO EFFECTS OF QUATERNARY NEUROLEPTICS ON HUMAN PROLACTIN AND ADENYLCYCLASE SIR,—Quaternary ammonium salts of neuroleptic drugs cannot penetrate the blood/brain barrier in significant amounts. Thus they could be valuable tools for evaluating possible psychotropic effects of neuroleptics which might be triggered by the action of the drugs on structures outside the blood/brain barrier. Quaternary neuroleptics are roughly equipotent to their tertiary, conventional counterparts in behavioural tests in rats after microinjections into the central nervous system.’ Conventional tertiary neuroleptics inhibit dopamine-sensitive adenylcyclase activity2 and release prolactin in man,3 but are their quaternary counterparts equally effective?
Metal dentures and bridges
The charges for crowns, inlays, pinlays, and gold fillings would be £10 for each tooth restored, with a maximum of C30 if more than 3 teeth were restored; there would also be a maximum of C30 for a combination of any of these items of treatment. The special charges for particular high-cost items of treatment, such as crowns (which figured in about 3% of courses of treatment) had been introduced with reluctance, but this was the only way to keep the ordinary maximum charge down to a level which would not deter people from seeking
regular treatment. Optical charges would be raised from 2-25 to 2 90 for each single-vision lens, from 4-25 to £5.50 for each fused glass bifocal lens, and from ,5 to 6-15 for any other type of lens (including solid glass or plastic bifocals). Regulations implementing these proposals would be laid before Parliament to come into effect on April 1; the last increases in dental and optical charges came into effect on Jan. 1,1976. -
Blood for Private Patients
In answer to questions from Mr LAURIE PAVITT in the House of Commons on Feb. 8 concerning the use by private patients of blood collected by the National Blood Transfusion Service Mr ROLAND MOYLE, Minister of State, Department of Health and Social Security, said that no separate financial or administrative arrangements applied to blood used by private patients in N.H.S. hospitals. Daily charges were inclusive of accommodation and all services. Where blood was supplied to a private hospital or nursing home, no charge was made for the blood itself, but if circumstances justified, a charge might be made for the pathological and other services involved. Senior officials of the National Blood Transfusion Service were employees of the N.H.S. authorities. No instructions issued by the Department of Health barred them from serving on the board of directors of a private hospital or of organisations pro-
viding private-patient hospital cover.