, Volume 178, Issue 2–3, pp 296–302 | Cite as

Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition

  • Bankole A. Johnson
  • John D. Roache
  • Nassima Ait-Daoud
  • Christopher Wallace
  • Lynda T. Wells
  • Yanmei Wang
Original Investigation



While the effects of d-amphetamine in increasing performance have been established, there is a paucity of information on the effects of methamphetamine on cognition in drug-naive subjects, and no published information on the effects of intravenous methamphetamine administration in dependent individuals. The dihydropyridine-class calcium channel antagonist, isradipine, has been posited as a putative treatment to prevent methamphetamine-associated hypertensive crisis and its sequelae. Yet, isradipine’s effects on cognitive performance in methamphetamine-dependent individuals are not known.


Since individuals whose dependence on methamphetamine is attributable to the need to enhance performance may be loath to take a cognition-impairing medication, even for the treatment of life-threatening hypertensive crisis, it would be important to determine isradipine’s effects on performance.


We therefore examined in a blinded, placebo-controlled, crossover design the cognitive effects of low and high doses of intravenous methamphetamine (15 mg and 30 mg, respectively) in both the presence and absence of isradipine.


Intravenous d-methamphetamine produced dose-dependent increases in attention, concentration, and psychomotor performance. Isradipine, both with and without methamphetamine, had a modest effect to decrease attention.


Our results do not support the further testing of isradipine as a medication for improving the cognitive impairments that have been associated with chronic methamphetamine use.


Isradipine Methamphetamine Cognition Cognitive performance Attention Concentration Perceptual-motor function Dopamine Humans 


  1. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington D.C.Google Scholar
  2. Besson JA, Palin AN, Ebmeier KP, Eagles JM (1988) Calcium antagonists and multi-infarct dementia: a trial involving sequential NMR and psychometric assessment. Int J Geriatr Psychiatry 3:99–105Google Scholar
  3. Birkenhager WH, de Leeuw PW, Staessen JA, Wang JG, Forette F, Seux ML (2000) Cognitive impairment and dementia in hypertension; the effect of antihypertensive medication [in Dutch]. Ned Tijdschr Geneeskd 144:1469–1474PubMedGoogle Scholar
  4. Brecht M-L, O’Brien A, von Mayrhauser C, Anglin MD (2004) Methamphetamine use behaviors and gender differences. Addict Behav 29:89–106CrossRefPubMedGoogle Scholar
  5. Cole BJ, Robbins TW (1987) Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic–noradrenergic interactions. Psychopharmacology 91:458–466PubMedGoogle Scholar
  6. Cole BJ, Robbins TW (1992) Forebrain norepinephrine: role in controlled information processing in the rat. Neuropsychopharmacology 7:129–142PubMedGoogle Scholar
  7. De Vries DJ, Beart PM (1984) Competitive inhibition of [3H]spiperone binding to D-2 dopamine receptors in striatal homogenates by organic calcium channel antagonists and polyvalent cations. Eur J Pharmacol 106:133–139CrossRefPubMedGoogle Scholar
  8. Denolle T, Sassano P, Allain H, Bentué-Ferrer D, Breton S, Cimarosti I, Ouatara B, Merienne M, Gandon J-M (2002) Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients. Fundam Clin Pharmacol 16:527–535CrossRefPubMedGoogle Scholar
  9. Di Paolo T (1994) Modulation of brain dopamine transmission by sex steroids. Rev Neurosci 5:27–41PubMedGoogle Scholar
  10. Drachman DA (1977) Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 27:783–790PubMedGoogle Scholar
  11. Ernst T, Chang L, Leonido-Yee M, Speck O (2000) Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1H MRS study. Neurology 54:1344–1349PubMedGoogle Scholar
  12. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhager WH, Babarskiene MR, Babeanu S, Bossini A, Gil-Extremera B, Girerd X, Laks T, Lilov E, Moisseyev V, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Fagard R (1998) Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 352:1347–1351CrossRefPubMedGoogle Scholar
  13. Ginsberg MD, Lin B, Morikawa E, Dietrich WD, Busto R, Globus MY (1991) Calcium antagonists in the treatment of experimental cerebral ischemia. Arzneimittelforschung 41:334–337PubMedGoogle Scholar
  14. Gunne LM (1977) Effects of amphetamine in humans. In: Martin WR (ed) Drug addiction II: amphetamine, psychotogen, and marihuana dependence. Springer, Berlin Heidelberg New York, pp 247–275Google Scholar
  15. Harvey JA (1987) Behavioral pharmacology of central nervous system stimulants. Neuropharmacology 26:887–892CrossRefPubMedGoogle Scholar
  16. Heidrich A, Rosler M, Riederer P (1997) Pharmacotherapy of Alzheimer dementia: therapy of cognitive symptoms—new results of clinical studies [German]. Fortschr Neurol Psychiatr 65:108–121PubMedGoogle Scholar
  17. Hunt D (1995) Pulse check: national trends in drug abuse. Office of National Drug Control Policy, Washington D.C.Google Scholar
  18. Johnson BA, Oldman D, Goodall EM, Chen YR, Cowen PJ (1996) Effects of GR 68755 on d-amphetamine-induced changes in mood, cognitive performance, appetite, food preference, and caloric and macronutrient intake in humans. Behav Pharmacol 7:216–227PubMedGoogle Scholar
  19. Johnson BA, Ait-Daoud N, Wells LT (2000) Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced cognitive and physiological changes in humans. Neuropsychopharmacology 22:504–512CrossRefPubMedGoogle Scholar
  20. King TS, Steger RW, Morgan WW (1986) Effect of ovarian steroids to stimulate region-specific hypothalamic 5-hydroxytryptamine synthesis in ovariectomized rats. Neuroendocrinology 42:344–350PubMedGoogle Scholar
  21. Lee EHY, Lin WR (1991) Nifedipine and verapamil block the memory-facilitating effect of corticotropin-releasing factor in rats. Life Sci 48:1333–1340CrossRefPubMedGoogle Scholar
  22. Lepakhin VK, Ivleva AI, Romashova MF, Udotova SA, Zubovskii LG (1992) The effect of isradipine on the central and cerebral hemodynamics of patients with circulatory encephalopathy and hypertension [in Russian]. Eksp Klin Farmakol 55:24–26Google Scholar
  23. LeVere SD, LeVere TE (1994) Old age and cognition: evaluation of a human short-term memory test with nonhuman primates and the memory-enhancing effects of nimodipine. Psychobiology 22:106–111Google Scholar
  24. Levy A, Kong RM, Stillman MJ, Shukitt-Hale B, Kadar T, Rauch TM, Lieberman HR (1991) Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats. Pharmacol Biochem Behav 39:781–786CrossRefPubMedGoogle Scholar
  25. von Mayrhauser C, Brecht M-L, Anglin MD (2002) Use ecology and drug use motivations of methamphetamine users admitted to substance abuse treatment facilities in Los Angeles: an emerging profile. J Addict Dis 21:45–60PubMedGoogle Scholar
  26. McLeod DR, Griffiths RR, Bigelow GE, Yingling J (1982) An automated version of the digit symbol substitution test (DSST). Behav Res Methods Instrum Comput 14:463–466Google Scholar
  27. McTavish SF, McPherson MH, Harmer CJ, Clark L, Sharp T, Goodwin GM, Cowen PJ (2001) Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and patients with manic illness. Br J Psychiatry 179:356–360CrossRefPubMedGoogle Scholar
  28. Mintzer MZ, Guarino J, Kirk T, Roache JD, Griffiths RR (1997) Ethanol and pentobarbital: comparison of behavioral and subjective effects in sedative drug abusers. Exp Clin Psychopharmacol 5:203–215CrossRefPubMedGoogle Scholar
  29. Nakane H, Ooboshi H, Ibayashi S, Yao H, Sadoshima S, Fujishima M (1995) Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats. Neurosci Lett 188:151–154CrossRefPubMedGoogle Scholar
  30. Quevedo J, Vianna M, Daroit D, Born AG, Kuyven CR, Roesler R, Quillfeldt JA (1998) L-type voltage-dependent calcium channel blocker nifedipine enhances memory retention when infused into the hippocampus. Neurobiol Learn Mem 69:320–325Google Scholar
  31. Rawson RA, McCann MJ, Hasson AJ, Ling W (2000) Addiction pharmacotherapy 2000: new options, new challenges. J Psychoact Drugs 32:371–378Google Scholar
  32. Roache JD, Cherek DR, Bennett RH, Schenkler JC, Cowan KA (1993) Differential effects of triazolam and ethanol on awareness, memory, and psychomotor performance. J Clin Psychopharmacol 13:3–15PubMedGoogle Scholar
  33. Rudin M, Sauter A, Wiederhold KH (1987) Application of NMR imaging and spectroscopy to the pharmacology of cerebro-vascular disorders. Therapie 42:477–481PubMedGoogle Scholar
  34. Salo R, Nordahl TE, Possin K, Leamon M, Gibson DR, Galloway GP, Flynn NM, Henik A, Pfefferbaum A, Sullivan EV (2002) Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals. Psychiatry Res 111:65–74CrossRefPubMedGoogle Scholar
  35. SAS Institute, Inc. (2002) SAS user’s guide: statistics, version 9.00. SAS Institute, Inc., Cary, NCGoogle Scholar
  36. Sauter A, Rudin M (1986) Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging. Stroke 17:1228–1234Google Scholar
  37. Sauter A, Rudin M, Wiederhold KH (1988) Reduction of neural damage in irreversible cerebral ischemia by calcium antagonists. Neurochem Pathol 9:211–236PubMedGoogle Scholar
  38. Schwartz BL, Fay-McCarthy M, Kendrick K, Rosse RB, Deutsch SI (1997) Effects of nifedipine, a calcium channel antagonist, on cognitive function in schizophrenic patients with tardive dyskinesia. Clin Neuropharmacol 20:364–370PubMedGoogle Scholar
  39. Silverstone PH, Oldman D, Johnson B, Cowen PJ (1992) Ondansetron, a 5-HT3 receptor antagonist, partially attenuates the effects of amphetamine: a pilot study in healthy volunteers. Int Clin Psychopharmacol 7:37–43Google Scholar
  40. Spiegel R (1979) Effects of amphetamines on performance and on polygraphic sleep parameters in man. In: Passouant P, Oswald I (eds) Pharmacology of the states of alertness. Pergamon, Oxford, pp 189–201Google Scholar
  41. Taya K, Watanabe Y, Kobayashi H, Fujiwara M (2000) Nimodipine improves the disruption of spatial cognition induced by cerebral ischemia. Physiol Behav 70:19–25CrossRefPubMedGoogle Scholar
  42. Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Le JY, Toga AW, Ling W, London ED (2004) Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 24:6028–6036Google Scholar
  43. US Department of Health and Human Services (2001) The DAWN report. The Substance Abuse and Mental Health Services Administration (SAMHSA), Drug Abuse Warning Network (DAWN), Washington D.C.Google Scholar
  44. Vetulani J, Battaglia M, Sansone M (1997) Nimodipine on shuttle-box avoidance learning in mice: no impairment but slight improvement. Pharmacol Biochem Behav 56:577–581CrossRefPubMedGoogle Scholar
  45. Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding YS, Logan J, Wong C, Miller EN (2001) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158:377–382CrossRefPubMedGoogle Scholar
  46. Weiss B, Laties VG (1962) Enhancement of human performance by caffeine and the amphetamines. Pharmacol Rev 14:1–36PubMedGoogle Scholar
  47. Yamada S, Uchida S, Ohkura T, Kimura R, Yamaguchi M, Suzuki M, Yamamoto M (1996) Alterations in calcium antagonist receptors and calcium content in senescent brain and attenuation by nimodipine and nicardipine. J Pharmacol Exp Ther 277:721–727PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Bankole A. Johnson
    • 1
  • John D. Roache
    • 1
  • Nassima Ait-Daoud
    • 1
  • Christopher Wallace
    • 1
  • Lynda T. Wells
    • 2
  • Yanmei Wang
    • 1
  1. 1.Department of PsychiatryThe University of Texas Health Science Center at San AntonioSan AntonioUSA
  2. 2.Department of AnesthesiologyThe University of Texas Health Science Center at San AntonioSan AntonioUSA

Personalised recommendations